Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

The Role of a Neurovascular Signaling Pathway Involving Hypoxia-Inducible Factor and Notch in the Function of the Central Nervous System

  • Kim, Seunghee (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Lee, Minjae (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Choi, Yoon Kyung (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2019.07.19
  • Accepted : 2019.08.12
  • Published : 2019.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

In the neurovascular unit, the neuronal and vascular systems communicate with each other. O2 and nutrients, reaching endothelial cells (ECs) through the blood stream, spread into neighboring cells, such as neural stem cells, and neurons. The proper function of neural circuits in adults requires sufficient O2 and glucose for their metabolic demands through angiogenesis. In a central nervous system (CNS) injury, such as glioma, Parkinson's disease, and Alzheimer's disease, damaged ECs can contribute to tissue hypoxia and to the consequent disruption of neuronal functions and accelerated neurodegeneration. This review discusses the current evidence regarding the contribution of oxygen deprivation to CNS injury, with an emphasis on hypoxia-inducible factor (HIF)-mediated pathways and Notch signaling. Additionally, it focuses on adult neurological functions and angiogenesis, as well as pathological conditions in the CNS. Furthermore, the functional interplay between HIFs and Notch is demonstrated in pathophysiological conditions.

Keywords

References

  1. Ables, J. L., Breunig, J. J., Eisch, A. J. and Rakic, P. (2011) Not(ch) just development: Notch signalling in the adult brain. Nat. Rev. Neurosci. 12, 269-283. https://doi.org/10.1038/nrn3024
  2. Andreu-Agullo, C., Morante-Redolat, J. M., Delgado, A. C. and Farinas, I. (2009) Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat. Neurosci. 12, 1514-1523. https://doi.org/10.1038/nn.2437
  3. Androutsellis-Theotokis, A., Leker, R. R., Soldner, F., Hoeppner, D. J., Ravin, R., Poser, S. W., Rueger, M. A., Bae, S. K., Kittappa, R. and McKay, R. D. (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442, 823-826. https://doi.org/10.1038/nature04940
  4. Ashok, B. S., Ajith, T. A. and Sivanesan, S. (2017) Hypoxia-inducible factors as neuroprotective agent in Alzheimer's disease. Clin. Exp. Pharmacol. Physiol. 44, 327-334. https://doi.org/10.1111/1440-1681.12717
  5. Austin, C. P., Feldman, D. E., Ida, J. A., Jr. and Cepko, C. L. (1995) Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch. Development 121, 3637-3650. https://doi.org/10.1242/dev.121.11.3637
  6. Bae, S. K., Kim, S. R., Kim, J. G., Kim, J. Y., Koo, T. H., Jang, H. O., Yun, I., Yoo, M. A. and Bae, M. K. (2006) Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1. FEBS Lett. 580, 4105-4113. https://doi.org/10.1016/j.febslet.2006.06.052
  7. Bae, Y. H., Joo, H., Bae, J., Hyeon, S. J., Her, S., Ko, E., Choi, H. G., Ryu, H., Hur, E. M., Bu, Y. and Lee, B. D. (2018) Brain injury induces HIF-1alpha-dependent transcriptional activation of LRRK2 that exacerbates brain damage. Cell Death Dis. 9, 1125. https://doi.org/10.1038/s41419-018-1180-y
  8. Bae, Y. H., Park, H. J., Kim, S. R., Kim, J. Y., Kang, Y., Kim, J. A., Wee, H. J., Kageyama, R., Jung, J. S., Bae, M. K. and Bae, S. K. (2011) Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis. Cardiovasc. Res. 89, 436-445. https://doi.org/10.1093/cvr/cvq276
  9. Baillieul, S., Chacaroun, S., Doutreleau, S., Detante, O., Pepin, J. L. and Verges, S. (2017) Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries? Exp. Biol. Med. (Maywood) 242, 1198-1206. https://doi.org/10.1177/1535370217712691
  10. Bar, E. E., Lin, A., Mahairaki, V., Matsui, W. and Eberhart, C. G. (2010) Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am. J. Pathol. 177, 1491-1502. https://doi.org/10.2353/ajpath.2010.091021
  11. Barteczek, P., Li, L., Ernst, A. S., Bohler, L. I., Marti, H. H. and Kunze, R. (2017) Neuronal HIF-1alpha and HIF-2alpha deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke. J. Cereb. Blood Flow Metab. 37, 291-306. https://doi.org/10.1177/0271678X15624933
  12. Batti, L., Taylor, C. T. and O’Connor, J. J. (2010) Hydroxylase inhibition reduces synaptic transmission and protects against a glutamateinduced ischemia in the CA1 region of the rat hippocampus. Neuroscience 167, 1014-1024. https://doi.org/10.1016/j.neuroscience.2010.03.011
  13. Bazzoni, R. and Bentivegna, A. (2019) Role of notch signaling pathway in glioblastoma pathogenesis. Cancers (Basel) 11, E292. https://doi.org/10.3390/cancers11030292
  14. Beaudry, M., Hidalgo, M., Launay, T., Bello, V. and Darribere, T. (2016) Regulation of myogenesis by environmental hypoxia. J. Cell Sci. 129, 2887-2896. https://doi.org/10.1242/jcs.188904
  15. Benedito, R. and Duarte, A. (2005) Expression of Dll4 during mouse embryogenesis suggests multiple developmental roles. Gene Expr. Patterns 5, 750-755. https://doi.org/10.1016/j.modgep.2005.04.004
  16. Benedito, R., Rocha, S. F., Woeste, M., Zamykal, M., Radtke, F., Casanovas, O., Duarte, A., Pytowski, B. and Adams, R. H. (2012) Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling. Nature 484, 110-114. https://doi.org/10.1038/nature10908
  17. Bentley, K., Gerhardt, H. and Bates, P. A. (2008) Agent-based simulation of notch-mediated tip cell selection in angiogenic sprout initialisation. J. Theor. Biol. 250, 25-36. https://doi.org/10.1016/j.jtbi.2007.09.015
  18. Berra, E., Benizri, E., Ginouves, A., Volmat, V., Roux, D. and Pouyssegur, J. (2003) HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J. 22, 4082-4090. https://doi.org/10.1093/emboj/cdg392
  19. Bertout, J. A., Patel, S. A., Fryer, B. H., Durham, A. C., Covello, K. L., Olive, K. P., Goldschmidt, M. H. and Simon, M. C. (2009) Heterozygosity for hypoxia inducible factor 1alpha decreases the incidence of thymic lymphomas in a p53 mutant mouse model. Cancer Res. 69, 3213-3220. https://doi.org/10.1158/0008-5472.CAN-08-4223
  20. Biron, K. E., Dickstein, D. L., Gopaul, R. and Jefferies, W. A. (2011) Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer’s disease. PLoS ONE 6, e23789. https://doi.org/10.1371/journal.pone.0023789
  21. Borggrefe, T., Lauth, M., Zwijsen, A., Huylebroeck, D., Oswald, F. and Giaimo, B. D. (2016) The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFbeta/BMP and hypoxia pathways. Biochim. Biophys. Acta 1863, 303-313. https://doi.org/10.1016/j.bbamcr.2015.11.020
  22. Bradshaw, A., Wickremsekera, A., Tan, S. T., Peng, L., Davis, P. F. and Itinteang, T. (2016) Cancer stem cell hierarchy in glioblastoma multiforme. Front. Surg. 3, 21.
  23. Braun, S. M. and Jessberger, S. (2014) Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function. Neuropathol. Appl. Neurobiol. 40, 3-12. https://doi.org/10.1111/nan.12107
  24. Bray, S. J. (2006) Notch signalling: a simple pathway becomes complex. Nat. Rev. Mol. Cell Biol. 7, 678-689. https://doi.org/10.1038/nrm2009
  25. Bruick, R. K. and McKnight, S. L. (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294, 1337-1340. https://doi.org/10.1126/science.1066373
  26. Carrica, L., Li, L., Newville, J., Kenton, J., Gustus, K., Brigman, J. and Cunningham, L. A. (2019) Genetic inactivation of hypoxia inducible factor 1-alpha (HIF-1alpha) in adult hippocampal progenitors impairs neurogenesis and pattern discrimination learning. Neurobiol. Learn. Mem. 157, 79-85. https://doi.org/10.1016/j.nlm.2018.12.002
  27. Chai, X., Kong, W., Liu, L., Yu, W., Zhang, Z. and Sun, Y. (2014) A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis. Neural. Regen. Res. 9, 1145-1153. https://doi.org/10.4103/1673-5374.135317
  28. Choi, Y. K. (2017) A positive circuit of VEGF increases Glut-1 expression by increasing HIF-1alpha gene expression in human retinal endothelial cells. Arch. Pharm. Res. 40, 1433-1442. https://doi.org/10.1007/s12272-017-0971-5
  29. Choi, Y. K., Kim, C. K., Lee, H., Jeoung, D., Ha, K. S., Kwon, Y. G., Kim, K. W. and Kim, Y. M. (2010) Carbon monoxide promotes VEGF expression by increasing HIF-1alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF-1alpha protein. J. Biol. Chem. 285, 32116-32125. https://doi.org/10.1074/jbc.M110.131284
  30. Choi, Y. K., Kim, J. H., Kim, W. J., Lee, H. Y., Park, J. A., Lee, S. W., Yoon, D. K., Kim, H. H., Chung, H., Yu, Y. S. and Kim, K. W. (2007) AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha. J. Neurosci. 27, 4472-4481. https://doi.org/10.1523/JNEUROSCI.5368-06.2007
  31. Choi, Y. K., Kim, J. H., Lee, D. K., Lee, K. S., Won, M. H., Jeoung, D., Lee, H., Ha, K. S., Kwon, Y. G. and Kim, Y. M. (2017) Carbon monoxide potentiation of l-type Ca2+ channel activity increases HIF-1alpha-independent VEGF expression via an AMPKalpha/SIRT1-mediated PGC-1alpha/ERRalpha axis. Antioxid. Redox Signal. 27, 21-36. https://doi.org/10.1089/ars.2016.6684
  32. Choi, Y. K., Park, J. H., Baek, Y. Y., Won, M. H., Jeoung, D., Lee, H., Ha, K. S., Kwon, Y. G. and Kim, Y. M. (2016) Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1alpha/ERRalpha activation. Biochem. Biophys. Res. Commun. 479, 297-304. https://doi.org/10.1016/j.bbrc.2016.09.063
  33. Choi, Y. K., Park, J. H., Yun, J. A., Cha, J. H., Kim, Y., Won, M. H., Kim, K. W., Ha, K. S., Kwon, Y. G. and Kim, Y. M. (2018) Heme oxygenase metabolites improve astrocytic mitochondrial function via a Ca2+-dependent HIF-1alpha/ERRalpha circuit. PLoS ONE 13, e0202039. https://doi.org/10.1371/journal.pone.0202039
  34. Chong, Z. Z., Li, F. and Maiese, K. (2005) Erythropoietin requires NF-kappaB and its nuclear translocation to prevent early and late apoptotic neuronal injury during beta-amyloid toxicity. Curr. Neurovasc. Res. 2, 387-399. https://doi.org/10.2174/156720205774962683
  35. Christian, K. M., Song, H. and Ming, G. L. (2014) Functions and dysfunctions of adult hippocampal neurogenesis. Annu. Rev. Neurosci. 37, 243-262. https://doi.org/10.1146/annurev-neuro-071013-014134
  36. Claxton, S. and Fruttiger, M. (2004) Periodic Delta-like 4 expression in developing retinal arteries. Gene Expr. Patterns 5, 123-127. https://doi.org/10.1016/j.modgep.2004.05.004
  37. Coleman, M. L., McDonough, M. A., Hewitson, K. S., Coles, C., Mecinovic, J., Edelmann, M., Cook, K. M., Cockman, M. E., Lancaster, D. E., Kessler, B. M., Oldham, N. J., Ratcliffe, P. J. and Schofield, C. J. (2007) Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J. Biol. Chem. 282, 24027-24038. https://doi.org/10.1074/jbc.M704102200
  38. Costa, R. M., Honjo, T. and Silva, A. J. (2003) Learning and memory deficits in Notch mutant mice. Curr. Biol. 13, 1348-1354. https://doi.org/10.1016/S0960-9822(03)00492-5
  39. Crews, L., Mizuno, H., Desplats, P., Rockenstein, E., Adame, A., Patrick, C., Winner, B., Winkler, J. and Masliah, E. (2008) Alphasynuclein alters Notch-1 expression and neurogenesis in mouse embryonic stem cells and in the hippocampus of transgenic mice. J. Neurosci. 28, 4250-4260. https://doi.org/10.1523/JNEUROSCI.0066-08.2008
  40. Cui, J. G., Fraser, P. E., St. George-Hyslop, P., Westaway, D. and Lukiw, W. J. (2004) Potential roles for presenilin-1 in oxygen sensing and in glial-specific gene expression. Neuroreport 15, 2025-2028. https://doi.org/10.1097/00001756-200409150-00006
  41. Cunningham, L. A., Candelario, K. and Li, L. (2012) Roles for HIF-1alpha in neural stem cell function and the regenerative response to stroke. Behav. Brain Res. 227, 410-417. https://doi.org/10.1016/j.bbr.2011.08.002
  42. De Strooper, B. and Konig, G. (1999) Alzheimer’s disease. A firm base for drug development. Nature 402, 471-472. https://doi.org/10.1038/44973
  43. Dengler, V. L., Galbraith, M. and Espinosa, J. M. (2014) Transcriptional regulation by hypoxia inducible factors. Crit. Rev. Biochem. Mol. Biol. 49, 1-15. https://doi.org/10.3109/10409238.2013.838205
  44. Desmond, D. W., Moroney, J. T., Sano, M. and Stern, Y. (2002) Incidence of dementia after ischemic stroke: results of a longitudinal study. Stroke 33, 2254-2260. https://doi.org/10.1161/01.STR.0000028235.91778.95
  45. Dietrich, L. S., Fuller, L., Yero, I. L. and Martinez, L. (1966) Nicotinamide mononucleotide pyrophosphorylase activity in animal tissues. J. Biol. Chem. 241, 188-191. https://doi.org/10.1016/S0021-9258(18)96977-2
  46. Diez, H., Fischer, A., Winkler, A., Hu, C. J., Hatzopoulos, A. K., Breier, G. and Gessler, M. (2007) Hypoxia-mediated activation of Dll4-Notch-Hey2 signaling in endothelial progenitor cells and adoption of arterial cell fate. Exp. Cell Res. 313, 1-9. https://doi.org/10.1016/j.yexcr.2006.09.009
  47. Dong, X., Wang, Y. S., Dou, G. R., Hou, H. Y., Shi, Y. Y., Zhang, R., Ma, K., Wu, L., Yao, L. B., Cai, Y. and Zhang, J. (2011) Influence of Dll4 via HIF-1alpha-VEGF signaling on the angiogenesis of choroidal neovascularization under hypoxic conditions. PLoS ONE 6, e18481. https://doi.org/10.1371/journal.pone.0018481
  48. Donoviel, D. B., Hadjantonakis, A. K., Ikeda, M., Zheng, H., Hyslop, P. S. and Bernstein, A. (1999) Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 13, 2801-2810. https://doi.org/10.1101/gad.13.21.2801
  49. Epstein, A. C., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O’Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., Tian, Y. M., Masson, N., Hamilton, D. L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P. H., Pugh, C. W., Schofield, C. J. and Ratcliffe, P. J. (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107, 43-54. https://doi.org/10.1016/S0092-8674(01)00507-4
  50. Estrach, S., Ambler, C. A., Lo Celso, C., Hozumi, K. and Watt, F. M. (2006) Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development 133, 4427-4438. https://doi.org/10.1242/dev.02644
  51. Fang, Y., Yu, S., Ma, Y., Sun, P., Ma, D., Ji, C. and Kong, B. (2013) Association of Dll4/notch and HIF-1a-VEGF signaling in the angiogenesis of missed abortion. PLoS ONE 8, e70667. https://doi.org/10.1371/journal.pone.0070667
  52. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J. and Moore, M. W. (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380, 439-442. https://doi.org/10.1038/380439a0
  53. Flugel, D., Gorlach, A., Michiels, C. and Kietzmann, T. (2007) Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization in a VHL-independent manner. Mol. Cell. Biol. 27, 3253-3265. https://doi.org/10.1128/MCB.00015-07
  54. Franklin, J. L., Berechid, B. E., Cutting, F. B., Presente, A., Chambers, C. B., Foltz, D. R., Ferreira, A. and Nye, J. S. (1999) Autonomous and non-autonomous regulation of mammalian neurite develop-ment by Notch1 and Delta1. Curr. Biol. 9, 1448-1457. https://doi.org/10.1016/S0960-9822(00)80114-1
  55. Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramsson, A., Jeltsch, M., Mitchell, C., Alitalo, K., Shima, D. and Betsholtz, C. (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163-1177. https://doi.org/10.1083/jcb.200302047
  56. Gridley, T. (2007) Notch signaling in vascular development and physiology. Development 134, 2709-2718. https://doi.org/10.1242/dev.004184
  57. Guo, C., Hao, L. J., Yang, Z. H., Chai, R., Zhang, S., Gu, Y., Gao, H. L., Zhong, M. L., Wang, T., Li, J. Y. and Wang, Z. Y. (2016) Deferoxamine-mediated up-regulation of HIF-1alpha prevents dopaminergic neuronal death via the activation of MAPK family proteins in MPTP-treated mice. Exp. Neurol. 280, 13-23. https://doi.org/10.1016/j.expneurol.2016.03.016
  58. Guo, L. H., Alexopoulos, P. and Perneczky, R. (2013) Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer's disease. Eur. Arch. Psychiatry Clin. Neurosci. 263, 553-560. https://doi.org/10.1007/s00406-013-0405-4
  59. Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U. and Bondesson, M. (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev. Cell 9, 617-628. https://doi.org/10.1016/j.devcel.2005.09.010
  60. Ha, T., Moon, K. H., Dai, L., Hatakeyama, J., Yoon, K., Park, H. S., Kong, Y. Y., Shimamura, K. and Kim, J. W. (2017) The retinal pigment epithelium is a notch signaling niche in the mouse retina. Cell Rep. 19, 351-363. https://doi.org/10.1016/j.celrep.2017.03.040
  61. Hamada, Y., Kadokawa, Y., Okabe, M., Ikawa, M., Coleman, J. R. and Tsujimoto, Y. (1999) Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development 126, 3415-3424. https://doi.org/10.1242/dev.126.15.3415
  62. Han, T., Yan, J., Chen, H., Ji, Y., Chen, J., Cui, J., Shen, W. and Zou, J. (2019) HIF-1alpha contributes to tube malformation of human lymphatic endothelial cells by upregulating VEGFR-3. Int. J. Oncol. 54, 139-151.
  63. Handler, M., Yang, X. and Shen, J. (2000) Presenilin-1 regulates neuronal differentiation during neurogenesis. Development 127, 2593-2606. https://doi.org/10.1242/dev.127.12.2593
  64. Harrington, L. S., Sainson, R. C., Williams, C. K., Taylor, J. M., Shi, W., Li, J. L. and Harris, A. L. (2008) Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc. Res. 75, 144-154. https://doi.org/10.1016/j.mvr.2007.06.006
  65. Hayashi, H. and Kume, T. (2008) Foxc transcription factors directly regulate Dll4 and Hey2 expression by interacting with the VEGFNotch signaling pathways in endothelial cells. PLoS ONE 3, e2401. https://doi.org/10.1371/journal.pone.0002401
  66. Herran, E., Perez-Gonzalez, R., Igartua, M., Pedraz, J. L., Carro, E. and Hernandez, R. M. (2015) Enhanced hippocampal neurogenesis in APP/Ps1 mouse model of Alzheimer's disease after implantation of VEGF-loaded PLGA nanospheres. Curr. Alzheimer Res. 12, 932-940. https://doi.org/10.2174/1567205012666151027121622
  67. Hewitson, K. S., McNeill, L. A., Riordan, M. V., Tian, Y. M., Bullock, A. N., Welford, R. W., Elkins, J. M., Oldham, N. J., Bhattacharya, S., Gleadle, J. M., Ratcliffe, P. J., Pugh, C. W. and Schofield, C. J. (2002) Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277, 26351-26355. https://doi.org/10.1074/jbc.C200273200
  68. Hu, Y. Y., Fu, L. A., Li, S. Z., Chen, Y., Li, J. C., Han, J., Liang, L., Li, L., Ji, C. C., Zheng, M. H. and Han, H. (2014) Hif-1alpha and Hif-2alpha differentially regulate Notch signaling through competitive interaction with the intracellular domain of Notch receptors in glioma stem cells. Cancer Lett. 349, 67-76. https://doi.org/10.1016/j.canlet.2014.03.035
  69. Hug, C. and Lodish, H. F. (2005) Medicine. Visfatin: a new adipokine. Science 307, 366-367. https://doi.org/10.1126/science.1106933
  70. Ikonomovic, M. D., Mi, Z. and Abrahamson, E. E. (2017) Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders. Ageing Res. Rev. 34, 51-63. https://doi.org/10.1016/j.arr.2016.11.003
  71. Imai, Y., Kobayashi, Y., Inoshita, T., Meng, H., Arano, T., Uemura, K., Asano, T., Yoshimi, K., Zhang, C. L., Matsumoto, G., Ohtsuka, T., Kageyama, R., Kiyonari, H., Shioi, G., Nukina, N., Hattori, N. and Takahashi, R. (2015) The Parkinson's disease-associated protein kinase LRRK2 modulates notch signaling through the endosomal pathway. PLoS Genet. 11, e1005503. https://doi.org/10.1371/journal.pgen.1005503
  72. Jaakkola, P., Mole, D. R., Tian, Y. M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A., Hebestreit, H. F., Mukherji, M., Schofield, C. J., Maxwell, P. H., Pugh, C. W. and Ratcliffe, P. J. (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by $O_2$-regulated prolyl hydroxylation. Science 292, 468-472. https://doi.org/10.1126/science.1059796
  73. Janelidze, S., Lindqvist, D., Francardo, V., Hall, S., Zetterberg, H., Blennow, K., Adler, C. H., Beach, T. G., Serrano, G. E., van Westen, D., Londos, E., Cenci, M. A. and Hansson, O. (2015) Increased CSF biomarkers of angiogenesis in Parkinson disease. Neurology 85, 1834-1842. https://doi.org/10.1212/WNL.0000000000002151
  74. Kadesch, T. (2004) Notch signaling: the demise of elegant simplicity. Curr. Opin. Genet. Dev. 14, 506-512. https://doi.org/10.1016/j.gde.2004.07.007
  75. Kalaria, R. N. (2000) The role of cerebral ischemia in Alzheimer's disease. Neurobiol. Aging 21, 321-330. https://doi.org/10.1016/S0197-4580(00)00125-1
  76. Kalaria, R. N., Cohen, D. L., Premkumar, D. R., Nag, S., LaManna, J. C. and Lust, W. D. (1998) Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. Brain Res. Mol. Brain Res. 62, 101-105. https://doi.org/10.1016/S0169-328X(98)00190-9
  77. Kanamori, M., Kawaguchi, T., Nigro, J. M., Feuerstein, B. G., Berger, M. S., Miele, L. and Pieper, R. O. (2007) Contribution of Notch signaling activation to human glioblastoma multiforme. J. Neurosurg. 106, 417-427. https://doi.org/10.3171/jns.2007.106.3.417
  78. Kim, D. H., Yoon, H. J., Cha, Y. N. and Surh, Y. J. (2018) Role of heme oxygenase-1 and its reaction product, carbon monoxide, in manifestation of breast cancer stem cell-like properties: Notch-1 as a putative target. Free Radic. Res. 52, 1336-1347. https://doi.org/10.1080/10715762.2018.1473571
  79. Kim, Y., Park, J. and Choi, Y. K. (2019) The role of astrocytes in the central nervous system focused on BK channel and heme oxygenase metabolites: A review. Antioxidants (Basel) 8, 121. https://doi.org/10.3390/antiox8050121
  80. Klein, W. L. (2013) Synaptotoxic amyloid-beta oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer's disease? J. Alzheimers Dis. 33 Suppl 1, S49-S65. https://doi.org/10.3233/JAD-2012-129039
  81. Koivunen, P., Tiainen, P., Hyvarinen, J., Williams, K. E., Sormunen, R., Klaus, S. J., Kivirikko, K. I. and Myllyharju, J. (2007) An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. J. Biol. Chem. 282, 30544-30552. https://doi.org/10.1074/jbc.M704988200
  82. Krebs, L. T., Deftos, M. L., Bevan, M. J. and Gridley, T. (2001) The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionally regulated by the notch signaling pathway. Dev. Biol. 238, 110-119. https://doi.org/10.1006/dbio.2001.0408
  83. Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C. and Kintner, C. (2001) Nrarp is a novel intracellular component of the Notch signaling pathway. Genes Dev. 15, 1885-1899. https://doi.org/10.1101/gad.908101
  84. Lang, A. E. (2011) A critical appraisal of the premotor symptoms of Parkinson's disease: Potential usefulness in early diagnosis and design of neuroprotective trials. Mov. Disord. 26, 775-783. https://doi.org/10.1002/mds.23609
  85. Lathia, J. D., Mattson, M. P. and Cheng, A. (2008) Notch: From neural development to neurological disorders. J. Neurochem. 107, 1471-1481. https://doi.org/10.1111/j.1471-4159.2008.05715.x
  86. Lee, H. and Choi, Y. K. (2018) Regenerative effects of heme oxygenase metabolites on neuroinflammatory diseases. Int J Mol Sci 20, E78. https://doi.org/10.3390/ijms20010078
  87. Lee, J. H., Suk, J., Park, J., Kim, S. B., Kwak, S. S., Kim, J. W., Lee, C. H., Byun, B., Ahn, J. K. and Joe, C. O. (2009) Notch signal activates hypoxia pathway through HES1-dependent SRC/signal transducers and activators of transcription 3 pathway. Mol. Cancer Res. 7, 1663-1671. https://doi.org/10.1158/1541-7786.MCR-09-0191
  88. Lee, S., Chen, T. T., Barber, C. L., Jordan, M. C., Murdock, J., Desai, S., Ferrara, N., Nagy, A., Roos, K. P. and Iruela-Arispe, M. L. (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130, 691-703. https://doi.org/10.1016/j.cell.2007.06.054
  89. Li, L., Candelario, K. M., Thomas, K., Wang, R., Wright, K., Messier, A. and Cunningham, L. A. (2014) Hypoxia inducible factor-1alpha (HIF-1alpha) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ. J. Neurosci. 34, 16713-16719. https://doi.org/10.1523/JNEUROSCI.4590-13.2014
  90. Li, Y., Wu, L., Yu, M., Yang, F., Wu, B., Lu, S., Tu, M. and Xu, H. (2018) HIF-1alpha is critical for the activation of notch signaling in neurogenesis during acute epilepsy. Neuroscience 394, 206-219. https://doi.org/10.1016/j.neuroscience.2018.10.037
  91. Liu, J., Zhang, C., Zhao, Y., Yue, X., Wu, H., Huang, S., Chen, J., Tomsky, K., Xie, H., Khella, C. A., Gatza, M. L., Xia, D., Gao, J., White, E., Haffty, B. G., Hu, W. and Feng, Z. (2017) Parkin targets HIF-1alpha for ubiquitination and degradation to inhibit breast tumor progression. Nat. Commun. 8, 1823. https://doi.org/10.1038/s41467-017-01947-w
  92. Liu, Y., Liu, F., Iqbal, K., Grundke-Iqbal, I. and Gong, C. X. (2008) Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett. 582, 359-364. https://doi.org/10.1016/j.febslet.2007.12.035
  93. Liu, Y. V., Baek, J. H., Zhang, H., Diez, R., Cole, R. N. and Semenza, G. L. (2007) RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitorinduced degradation of HIF-1alpha. Mol. Cell 25, 207-217. https://doi.org/10.1016/j.molcel.2007.01.001
  94. Liu, Y. V. and Semenza, G. L. (2007) RACK1 vs. HSP90: Competition for HIF-1 alpha degradation vs. stabilization. Cell Cycle 6, 656-659. https://doi.org/10.4161/cc.6.6.3981
  95. Liu, Z. J., Shirakawa, T., Li, Y., Soma, A., Oka, M., Dotto, G. P., Fairman, R. M., Velazquez, O. C. and Herlyn, M. (2003) Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis. Mol. Cell. Biol. 23, 14-25. https://doi.org/10.1128/MCB.23.1.14-25.2003
  96. Lo, E. H. and Rosenberg, G. A. (2009) The neurovascular unit in health and disease: Introduction. Stroke 40, S2-S3. https://doi.org/10.1161/STROKEAHA.108.534404
  97. Lobov, I. B., Renard, R. A., Papadopoulos, N., Gale, N. W., Thurston, G., Yancopoulos, G. D. and Wiegand, S. J. (2007) Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc. Natl. Acad. Sci. U.S.A. 104, 3219-3224. https://doi.org/10.1073/pnas.0611206104
  98. Logeat, F., Bessia, C., Brou, C., LeBail, O., Jarriault, S., Seidah, N. G. and Israel, A. (1998) The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc. Natl. Acad. Sci. U.S.A. 95, 8108-8112. https://doi.org/10.1073/pnas.95.14.8108
  99. Lopez-Juarez, A., Titus, H. E., Silbak, S. H., Pressler, J. W., Rizvi, T. A., Bogard, M., Bennett, M. R., Ciraolo, G., Williams, M. T., Vorhees, C. V. and Ratner, N. (2017) Oligodendrocyte Nf1 controls aberrant notch activation and regulates myelin structure and behavior. Cell Rep. 19, 545-557. https://doi.org/10.1016/j.celrep.2017.03.073
  100. Louvi, A. and Artavanis-Tsakonas, S. (2006) Notch signalling in vertebrate neural development. Nature reviews. Neuroscience 7, 93-102.
  101. Lucking, C. B., Durr, A., Bonifati, V., Vaughan, J., De Michele, G., Gasser, T., Harhangi, B. S., Meco, G., Denefle, P., Wood, N. W., Agid, Y. and Brice, A.; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease (2000) Association between early-onset Parkinson's disease and mutations in the parkin gene. N. Engl. J. Med. 342, 1560-1567. https://doi.org/10.1056/NEJM200005253422103
  102. Luo, L. and O'Leary, D. D. (2005) Axon retraction and degeneration in development and disease. Annu. Rev. Neurosci. 28, 127-156. https://doi.org/10.1146/annurev.neuro.28.061604.135632
  103. Lutolf, S., Radtke, F., Aguet, M., Suter, U. and Taylor, V. (2002) Notch1 is required for neuronal and glial differentiation in the cerebellum. Development 129, 373-385. https://doi.org/10.1242/dev.129.2.373
  104. Majmundar, A. J., Wong, W. J. and Simon, M. C. (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40, 294-309. https://doi.org/10.1016/j.molcel.2010.09.022
  105. Maki, T., Maeda, M., Uemura, M., Lo, E. K., Terasaki, Y., Liang, A. C., Shindo, A., Choi, Y. K., Taguchi, A., Matsuyama, T., Takahashi, R., Ihara, M. and Arai, K. (2015) Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter. Neurosci. Lett. 597, 164-169. https://doi.org/10.1016/j.neulet.2015.04.047
  106. Man, J., Yu, X., Huang, H., Zhou, W., Xiang, C., Huang, H., Miele, L., Liu, Z., Bebek, G., Bao, S. and Yu, J. S. (2018) Hypoxic induction of vasorin regulates Notch1 turnover to maintain glioma stem-like cells. Cell Stem Cell 22, 104-118.E6. https://doi.org/10.1016/j.stem.2017.10.005
  107. Mason, H. A., Rakowiecki, S. M., Gridley, T. and Fishell, G. (2006) Loss of notch activity in the developing central nervous system leads to increased cell death. Dev. Neurosci. 28, 49-57. https://doi.org/10.1159/000090752
  108. Mazumdar, J., O'Brien, W. T., Johnson, R. S., LaManna, J. C., Chavez, J. C., Klein, P. S. and Simon, M. C. (2010) $O_2$ regulates stem cells through Wnt/beta-catenin signalling. Nat. Cell Biol. 12, 1007-1013. https://doi.org/10.1038/ncb2102
  109. Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T. and Kaelin, W. G., Jr. (2008) Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood 111, 3236-3244. https://doi.org/10.1182/blood-2007-10-117812
  110. Mottet, D., Dumont, V., Deccache, Y., Demazy, C., Ninane, N., Raes, M. and Michiels, C. (2003) Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta pathway in HepG2 cells. J. Biol. Chem. 278, 31277-31285. https://doi.org/10.1074/jbc.M300763200
  111. Muoio, V., Persson, P. B. and Sendeski, M. M. (2014) The neurovascular unit-concept review. Acta Physiol. (Oxf.) 210, 790-798. https://doi.org/10.1111/apha.12250
  112. Ogunshola, O. O. and Antoniou, X. (2009) Contribution of hypoxia to Alzheimer's disease: Is HIF-1alpha a mediator of neurodegeneration? Cell. Mol. Life Sci. 66, 3555-3563. https://doi.org/10.1007/s00018-009-0141-0
  113. Phng, L. K. and Gerhardt, H. (2009) Angiogenesis: A team effort coordinated by notch. Dev. Cell 16, 196-208. https://doi.org/10.1016/j.devcel.2009.01.015
  114. Pistollato, F., Rampazzo, E., Persano, L., Abbadi, S., Frasson, C., Denaro, L., D’Avella, D., Panchision, D. M., Della Puppa, A., Scienza, R. and Basso, G. (2010) Interaction of hypoxia-inducible factor-1alpha and Notch signaling regulates medulloblastoma precursor proliferation and fate. Stem Cells 28, 1918-1929. https://doi.org/10.1002/stem.518
  115. Pitulescu, M. E., Schmidt, I., Giaimo, B. D., Antoine, T., Berkenfeld, F., Ferrante, F., Park, H., Ehling, M., Biljes, D., Rocha, S. F., Langen, U. H., Stehling, M., Nagasawa, T., Ferrara, N., Borggrefe, T. and Adams, R. H. (2017) Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nat. Cell Biol. 19, 915-927. https://doi.org/10.1038/ncb3555
  116. Religa, P., Cao, R., Religa, D., Xue, Y., Bogdanovic, N., Westaway, D., Marti, H. H., Winblad, B. and Cao, Y. (2013) VEGF significantly restores impaired memory behavior in Alzheimer's mice by improvement of vascular survival. Sci. Rep. 3, 2053. https://doi.org/10.1038/srep02053
  117. Roitbak, T., Li, L. and Cunningham, L. A. (2008) Neural stem/progenitor cells promote endothelial cell morphogenesis and protect endothelial cells against ischemia via HIF-1alpha-regulated VEGF signaling. J. Cereb. Blood Flow Metab. 28, 1530-1542. https://doi.org/10.1038/jcbfm.2008.38
  118. Roitbak, T., Surviladze, Z. and Cunningham, L. A. (2011) Continuous expression of HIF-1alpha in neural stem/progenitor cells. Cell. Mol. Neurobiol. 31, 119-133. https://doi.org/10.1007/s10571-010-9561-5
  119. Samal, B., Sun, Y., Stearns, G., Xie, C., Suggs, S. and McNiece, I. (1994) Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol. Cell. Biol. 14, 1431-1437. https://doi.org/10.1128/MCB.14.2.1431
  120. Saura, C. A., Choi, S. Y., Beglopoulos, V., Malkani, S., Zhang, D., Shankaranarayana Rao, B. S., Chattarji, S., Kelleher, R. J., 3rd, Kandel, E. R., Duff, K., Kirkwood, A. and Shen, J. (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42, 23-36. https://doi.org/10.1016/S0896-6273(04)00182-5
  121. Semenza, G. L. (2003) Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3, 721-732. https://doi.org/10.1038/nrc1187
  122. Semenza, G. L. (2007) Life with oxygen. Science 318, 62-64. https://doi.org/10.1126/science.1147949
  123. Seymour, T., Nowak, A. and Kakulas, F. (2015) Targeting aggressive cancer stem cells in glioblastoma. Front. Oncol. 5, 159.
  124. Shim, J. W. and Madsen, J. R. (2018) VEGF signaling in neurological disorders. Int. J. Mol. Sci. 19, E275. https://doi.org/10.3390/ijms19010275
  125. Shingo, T., Sorokan, S. T., Shimazaki, T. and Weiss, S. (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J. Neurosci. 21, 9733-9743. https://doi.org/10.1523/JNEUROSCI.21-24-09733.2001
  126. Shutter, J. R., Scully, S., Fan, W., Richards, W. G., Kitajewski, J., Deblandre, G. A., Kintner, C. R. and Stark, K. L. (2000) Dll4, a novel Notch ligand expressed in arterial endothelium. Genes Dev. 14, 1313-1318.
  127. Snowdon, D. A., Greiner, L. H., Mortimer, J. A., Riley, K. P., Greiner, P. A. and Markesbery, W. R. (1997) Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 277, 813-817. https://doi.org/10.1001/jama.1997.03540340047031
  128. Soucek, T., Cumming, R., Dargusch, R., Maher, P. and Schubert, D. (2003) The regulation of glucose metabolism by HIF-1 mediates a neuroprotective response to amyloid beta peptide. Neuron 39, 43-56. https://doi.org/10.1016/S0896-6273(03)00367-2
  129. Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., Bostrom, E., Westerlund, I., Vial, C., Buchholz, B. A., Possnert, G., Mash, D. C., Druid, H. and Frisen, J. (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219-1227. https://doi.org/10.1016/j.cell.2013.05.002
  130. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R. and Goedert, M. (1997) Alpha-synuclein in Lewy bodies. Nature 388, 839-840. https://doi.org/10.1038/42166
  131. Spuch, C., Antequera, D., Portero, A., Orive, G., Hernandez, R. M., Molina, J. A., Bermejo-Pareja, F., Pedraz, J. L. and Carro, E. (2010) The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease. Biomaterials 31, 5608-5618. https://doi.org/10.1016/j.biomaterials.2010.03.042
  132. Stone, J., Itin, A., Alon, T., Pe'er, J., Gnessin, H., Chan-Ling, T. and Keshet, E. (1995) Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J. Neurosci. 15, 4738-4747. https://doi.org/10.1523/JNEUROSCI.15-07-04738.1995
  133. Suchting, S., Freitas, C., le Noble, F., Benedito, R., Breant, C., Duarte, A. and Eichmann, A. (2007) The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc. Natl. Acad. Sci. U.S.A. 104, 3225-3230. https://doi.org/10.1073/pnas.0611177104
  134. Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L. E. and Song, W. (2006) Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc. Natl. Acad. Sci. U.S.A. 103, 18727-18732. https://doi.org/10.1073/pnas.0606298103
  135. Sun, Y., Jin, K., Xie, L., Childs, J., Mao, X. O., Logvinova, A. and Greenberg, D. A. (2003) VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J. Clin. Invest. 111, 1843-1851. https://doi.org/10.1172/JCI200317977
  136. Swiatek, P. J., Lindsell, C. E., del Amo, F. F., Weinmaster, G. and Gridley, T. (1994) Notch1 is essential for postimplantation development in mice. Genes Dev. 8, 707-719. https://doi.org/10.1101/gad.8.6.707
  137. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G. and Iwatsubo, T. (2003) The role of presenilin cofactors in the gamma-secretase complex. Nature 422, 438-441. https://doi.org/10.1038/nature01506
  138. Takeda, K., Ho, V. C., Takeda, H., Duan, L. J., Nagy, A. and Fong, G. H. (2006) Placental but not heart defects are associated with elevated hypoxia-inducible factor alpha levels in mice lacking prolyl hydroxylase domain protein 2. Mol. Cell. Biol. 26, 8336-8346. https://doi.org/10.1128/MCB.00425-06
  139. Tammela, T., Zarkada, G., Nurmi, H., Jakobsson, L., Heinolainen, K., Tvorogov, D., Zheng, W., Franco, C. A., Murtomaki, A., Aranda, E., Miura, N., Yla-Herttuala, S., Fruttiger, M., Makinen, T., Eichmann, A., Pollard, J. W., Gerhardt, H. and Alitalo, K. (2011) VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat. Cell Biol. 13, 1202-1213. https://doi.org/10.1038/ncb2331
  140. Tarkowski, E., Issa, R., Sjogren, M., Wallin, A., Blennow, K., Tarkowski, A. and Kumar, P. (2002) Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer's disease and vascular dementia. Neurobiol. Aging 23, 237-243. https://doi.org/10.1016/S0197-4580(01)00285-8
  141. Tong, Y., Yamaguchi, H., Giaime, E., Boyle, S., Kopan, R., Kelleher, R. J., 3rd and Shen, J. (2010) Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc. Natl. Acad. Sci. U.S.A. 107, 9879-9884. https://doi.org/10.1073/pnas.1004676107
  142. Vagnucci, A. H., Jr. and Li, W. W. (2003) Alzheimer’s disease and angiogenesis. Lancet 361, 605-608. https://doi.org/10.1016/S0140-6736(03)12521-4
  143. Villa, J. C., Chiu, D., Brandes, A. H., Escorcia, F. E., Villa, C. H., Maguire, W. F., Hu, C. J., de Stanchina, E., Simon, M. C., Sisodia, S. S., Scheinberg, D. A. and Li, Y. M. (2014) Nontranscriptional role of Hif-1alpha in activation of gamma-secretase and notch signaling in breast cancer. Cell Rep. 8, 1077-1092. https://doi.org/10.1016/j.celrep.2014.07.028
  144. Wakabayashi, N., Chartoumpekis, D. V. and Kensler, T. W. (2015) Crosstalk between Nrf2 and Notch signaling. Free Radic. Biol. Med. 88, 158-167. https://doi.org/10.1016/j.freeradbiomed.2015.05.017
  145. Wakamatsu, Y., Maynard, T. M., Jones, S. U. and Weston, J. A. (1999) NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1. Neuron 23, 71-81. https://doi.org/10.1016/S0896-6273(00)80754-0
  146. Wang, R., Zhang, Y. W., Zhang, X., Liu, R., Zhang, X., Hong, S., Xia, K., Xia, J., Zhang, Z. and Xu, H. (2006) Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia. FASEB J. 20, 1275-1277. https://doi.org/10.1096/fj.06-5839fje
  147. Wang, Y., Chan, S. L., Miele, L., Yao, P. J., Mackes, J., Ingram, D. K., Mattson, M. P. and Furukawa, K. (2004) Involvement of Notch signaling in hippocampal synaptic plasticity. Proc. Natl. Acad. Sci. U.S.A. 101, 9458-9462. https://doi.org/10.1073/pnas.0308126101
  148. Wang, Z., Hu, Y., Xiao, D., Wang, J., Liu, C., Xu, Y., Shi, X., Jiang, P., Huang, L., Li, P., Liu, H. and Qing, G. (2017) Stabilization of Notch1 by the Hsp90 chaperone is crucial for T-cell leukemogenesis. Clin. Cancer Res. 23, 3834-3846.
  149. Wei, Z., Chigurupati, S., Arumugam, T. V., Jo, D. G., Li, H. and Chan, S. L. (2011) Notch activation enhances the microglia-mediated inflammatory response associated with focal cerebral ischemia. Stroke 42, 2589-2594. https://doi.org/10.1161/STROKEAHA.111.614834
  150. Winklhofer, K. F. (2014) Parkin and mitochondrial quality control: toward assembling the puzzle. Trends Cell Biol. 24, 332-341. https://doi.org/10.1016/j.tcb.2014.01.001
  151. Winner, B., Regensburger, M., Schreglmann, S., Boyer, L., Prots, I., Rockenstein, E., Mante, M., Zhao, C., Winkler, J., Masliah, E. and Gage, F. H. (2012) Role of alpha-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus. J. Neurosci. 32, 16906-16916. https://doi.org/10.1523/JNEUROSCI.2723-12.2012
  152. Winner, B. and Winkler, J. (2015) Adult neurogenesis in neurodegenerative diseases. Cold Spring Harb. Perspect. Biol. 7, a021287. https://doi.org/10.1101/cshperspect.a021287
  153. Xia, D., Watanabe, H., Wu, B., Lee, S. H., Li, Y., Tsvetkov, E., Bolshakov, V. Y., Shen, J. and Kelleher, R. J., 3rd (2015) Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer’s disease. Neuron 85, 967-981. https://doi.org/10.1016/j.neuron.2015.02.010
  154. Xu, Q., Briggs, J., Park, S., Niu, G., Kortylewski, M., Zhang, S., Gritsko, T., Turkson, J., Kay, H., Semenza, G. L., Cheng, J. Q., Jove, R. and Yu, H. (2005) Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 24, 5552-5560. https://doi.org/10.1038/sj.onc.1208719
  155. Yoon, K. and Gaiano, N. (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat. Neurosci. 8, 709-715. https://doi.org/10.1038/nn1475
  156. Yuen, T. J., Silbereis, J. C., Griveau, A., Chang, S. M., Daneman, R., Fancy, S. P. J., Zahed, H., Maltepe, E. and Rowitch, D. H. (2014) Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell 158, 383-396. https://doi.org/10.1016/j.cell.2014.04.052
  157. Zhang, S., Zhang, Z., Sandhu, G., Ma, X., Yang, X., Geiger, J. D. and Kong, J. (2007) Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. Brain Res. 1138, 221-230. https://doi.org/10.1016/j.brainres.2006.12.086
  158. Zhang, X., Chen, T., Zhang, J., Mao, Q., Li, S., Xiong, W., Qiu, Y., Xie, Q. and Ge, J. (2012) Notch1 promotes glioma cell migration and invasion by stimulating beta-catenin and NF-kappaB signaling via AKT activation. Cancer Sci. 103, 181-190. https://doi.org/10.1111/j.1349-7006.2011.02154.x
  159. Zheng, X., Linke, S., Dias, J. M., Zheng, X., Gradin, K., Wallis, T. P., Hamilton, B. R., Gustafsson, M., Ruas, J. L., Wilkins, S., Bilton, R. L., Brismar, K., Whitelaw, M. L., Pereira, T., Gorman, J. J., Ericson, J., Peet, D. J., Lendahl, U. and Poellinger, L. (2008) Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. Proc. Natl. Acad. Sci. U.S.A. 105, 3368-3373. https://doi.org/10.1073/pnas.0711591105

Cited by

  1. Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System vol.21, pp.7, 2020, https://doi.org/10.3390/ijms21072273
  2. Proteomic Response of the Brain to Hypoxic Stress in Marine Medaka Fish (Oryzias melastigma) vol.8, 2020, https://doi.org/10.3389/fmars.2021.618489
  3. Epigenetic Regulation of Neuroinflammation in Parkinson’s Disease vol.22, pp.9, 2020, https://doi.org/10.3390/ijms22094956
  4. Repair Mechanisms of the Neurovascular Unit after Ischemic Stroke with a Focus on VEGF vol.22, pp.16, 2021, https://doi.org/10.3390/ijms22168543
  5. Differential gene expression indicates modulated responses to chronic and intermittent hypoxia in corallivorous fireworms (Hermodice carunculata) vol.11, pp.1, 2020, https://doi.org/10.1038/s41598-021-90540-9