Browse > Article
http://dx.doi.org/10.4062/biomolther.2021.012

Neuronal Autophagy: Characteristic Features and Roles in Neuronal Pathophysiology  

Valencia, McNeil (College of Pharmacy, Chung-Ang University)
Kim, Sung Rae (College of Pharmacy, Chung-Ang University)
Jang, Yeseul (College of Pharmacy, Chung-Ang University)
Lee, Sung Hoon (College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.29, no.6, 2021 , pp. 605-614 More about this Journal
Abstract
Autophagy is an important degradative pathway that eliminates misfolded proteins and damaged organelles from cells. Autophagy is crucial for neuronal homeostasis and function. A lack of or deficiency in autophagy leads to the accumulation of protein aggregates, which are associated with several neurodegenerative diseases. Compared with non-neuronal cells, neurons exhibit rapid autophagic flux because damaged organelles or protein aggregates cannot be diluted in post-mitotic cells; because of this, these cells exhibit characteristic features of autophagy, such as compartment-specific autophagy, which depends on polarized structures and rapid autophagy flux. In addition, neurons exhibit compartment-specific autophagy, which depends on polarized structures. Neuronal autophagy may have additional physiological roles other than amino acid recycling. In this review, we focus on the characteristics and regulatory factors of neuronal autophagy. We also describe intracellular selective autophagy in neurons and its association with neurodegenerative diseases.
Keywords
Neurons; Autophagy; Characteristic; Selective autophagy; Neurological disorder;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ge, P., Dawson, V. L. and Dawson, T. M. (2020) PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson's disease. Mol. Neurodegener. 15, 20.   DOI
2 Grishchuk, Y., Ginet, V., Truttmann, A. C., Clarke, P. G. and Puyal, J. (2011) Beclin 1-independent autophagy contributes to apoptosis in cortical neurons. Autophagy 7, 1115-1131.   DOI
3 Hoffmann-Conaway, S., Brockmann, M. M., Schneider, K., Annamneedi, A., Rahman, K. A., Bruns, C., Textoris-Taube, K., Trimbuch, T., Smalla, K. H., Rosenmund, C., Gundelfinger, E. D., Garner, C. C. and Montenegro-Venegas, C. (2020) Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice. eLife 9, e56590.   DOI
4 Berger, Z., Ravikumar, B., Menzies, F. M., Oroz, L. G., Underwood, B. R., Pangalos, M. N., Schmitt, I., Wullner, U., Evert, B. O., O'Kane, C. J. and Rubinsztein, D. C. (2006) Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 15, 433-442.   DOI
5 Bernard, A. and Klionsky, D. J. (2013) Autophagosome formation: tracing the source. Dev. Cell 25, 116-117.   DOI
6 Binotti, B., Pavlos, N. J., Riedel, D., Wenzel, D., Vorbruggen, G., Schalk, A. M., Kuhnel, K., Boyken, J., Erck, C., Martens, H., Chua, J. J. and Jahn, R. (2015) The GTPase Rab26 links synaptic vesicles to the autophagy pathway. eLife 4, e05597.   DOI
7 McEwan, D. G. and Dikic, I. (2011) The three musketeers of autophagy: phosphorylation, ubiquitylation and acetylation. Trends Cell Biol. 21, 195-201.   DOI
8 Metcalf, D. J., Garcia-Arencibia, M., Hochfeld, W. E. and Rubinsztein, D. C. (2012) Autophagy and misfolded proteins in neurodegeneration. Exp. Neurol. 238, 22-28.   DOI
9 Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T. and Ohsumi, Y. (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101-1111.   DOI
10 Wong, Y. C. and Holzbaur, E. L. (2014) Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagythat is disrupted by an ALS-linked mutation. Proc. Natl. Acad. Sci. U.S.A. 111, E4439- E4448.
11 Yamamoto, A. and Yue, Z. (2014) Autophagy and its normal and pathogenic states in the brain. Annu. Rev. Neurosci. 37, 55-78.   DOI
12 Yan, J., Porch, M. W., Court-Vazquez, B., Bennett, M. V. L. and Zukin, R. S. (2018) Activation of autophagy rescues synaptic and cognitive deficits in fragile X mice. Proc. Natl. Acad. Sci. U.S.A. 115, E9707-E9716.
13 Yap, C. C., Digilio, L., McMahon, L. P., Garcia, A. D. R. and Winckler, B. (2018) Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes. J. Cell Biol. 217, 3141-3159.   DOI
14 Deng, Z., Purtell, K., Lachance, V., Wold, M. S., Chen, S. and Yue, Z. (2017) Autophagy receptors and neurodegenerative diseases. Trends Cell Biol. 27, 491-504.   DOI
15 Maday, S. and Holzbaur, E. L. (2016) Compartment-specific regulation of autophagy in primary neurons. J. Neurosci. 36, 5933-5945.   DOI
16 Martinez-Vicente, M. (2017) Neuronal mitophagy in neurodegenerative diseases. Front. Mol. Neurosci. 10, 64.   DOI
17 Chung, W. S. and Barres, B. A. (2012) The role of glial cells in synapse elimination. Curr. Opin. Neurobiol. 22, 438-445.   DOI
18 Jiang, X., Litkowski, P. E., Taylor, A. A., Lin, Y., Snider, B. J. and Moulder, K. L. (2010) A role for the ubiquitin-proteasome system in activity-dependent presynaptic silencing. J. Neurosci. 30, 1798-1809.   DOI
19 Padamsey, Z., McGuinness, L., Bardo, S. J., Reinhart, M., Tong, R., Hedegaard, A., Hart, M. L. and Emptage, N. J. (2017) Activity-dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines. Neuron 93, 132-146.   DOI
20 Hori, I., Otomo, T., Nakashima, M., Miya, F., Negishi, Y., Shiraishi, H., Nonoda, Y., Magara, S., Tohyama, J., Okamoto, N., Kumagai, T., Shimoda, K., Yukitake, Y., Kajikawa, D., Morio, T., Hattori, A., Nakagawa, M., Ando, N., Nishino, I., Kato, M., Tsunoda, T., Saitsu, H., Kanemura, Y., Yamasaki, M., Kosaki, K., Matsumoto, N., Yoshimori, T. and Saitoh, S. (2017) Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement. Sci. Rep. 7, 3552.   DOI
21 Katsumata, K., Nishiyama, J., Inoue, T., Mizushima, N., Takeda, J. and Yuzaki, M. (2010) Dynein- and activity-dependent retrograde transport of autophagosomes in neuronal axons. Autophagy 6, 378-385.   DOI
22 Carloni, S., Buonocore, G. and Balduini, W. (2008) Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis. 32, 329-339.   DOI
23 Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M. and Tashiro, Y. (1991) Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J. Biol. Chem. 266, 17707-17712.   DOI
24 Young, J. E., Martinez, R. A. and La Spada, A. R. (2009) Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation. J. Biol. Chem. 284, 2363-2373.   DOI
25 Zatyka, M., Sarkar, S. and Barrett, T. (2020) Autophagy in rare (non-lysosomal) neurodegenerative diseases. J. Mol. Biol. 432, 2735-2753.   DOI
26 Carloni, S., Girelli, S., Scopa, C., Buonocore, G., Longini, M. and Balduini, W. (2010) Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 6, 366-377.   DOI
27 Xie, Z. and Klionsky, D. J. (2007) Autophagosome formation: core machinery and adaptations. Nat. Cell Biol. 9, 1102-1109.
28 Farias, G. G., Guardia, C. M., Britt, D. J., Guo, X. and Bonifacino, J. S. (2015) Sorting of dendritic and axonal vesicles at the pre-axonal exclusion zone. Cell Rep. 13, 1221-1232.   DOI
29 Gabryel, B., Kost, A. and Kasprowska, D. (2012) Neuronal autophagy in cerebral ischemia--a potential target for neuroprotective strategies? Pharmacol. Rep. 64, 1-15.   DOI
30 Ginty, D. D. and Segal, R. A. (2002) Retrograde neurotrophin signaling: Trk-ing along the axon. Curr. Opin. Neurobiol. 12, 268-274.   DOI
31 Corti, O., Blomgren, K., Poletti, A. and Beart, P. M. (2020) Autophagy in neurodegeneration: new insights underpinning therapy for neurological diseases. J. Neurochem. 154, 354-371.   DOI
32 Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E. and Tanaka, K. (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884.   DOI
33 Kononenko, N. L., Classen, G. A., Kuijpers, M., Puchkov, D., Maritzen, T., Tempes, A., Malik, A. R., Skalecka, A., Bera, S., Jaworski, J. and Haucke, V. (2017) Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. Nat. Commun. 8, 14819.   DOI
34 Kuijpers, M., Kochlamazashvili, G., Stumpf, A., Puchkov, D., Swaminathan, A., Lucht, M. T., Krause, E., Maritzen, T., Schmitz, D. and Haucke, V. (2020) Neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum. Neuron 109, 299-313.
35 Cheng, X. T., Zhou, B., Lin, M. Y., Cai, Q. and Sheng, Z. H. (2015) Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes. J. Cell Biol. 209, 377-386.   DOI
36 Chino, H. and Mizushima, N. (2020) ER-phagy: quality control and turnover of endoplasmic reticulum. Trends Cell Biol. 30, 384-398.   DOI
37 Erecinska, M., Cherian, S. and Silver, I. A. (2004) Energy metabolism in mammalian brain during development. Prog. Neurobiol. 73, 397-445.   DOI
38 Eskelinen, E. L. (2005) Maturation of autophagic vacuoles in mammalian cells. Autophagy 1, 1-10.   DOI
39 Mollereau, B. and Walter, L. (2019) Is WDR45 the missing link for ER stress-induced autophagy in beta-propeller associated neurodegeneration? Autophagy 15, 2163-2164.   DOI
40 Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y. and Yoshimori, T. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720-5728.   DOI
41 Zhu, C., Wang, X., Xu, F., Bahr, B. A., Shibata, M., Uchiyama, Y., Hagberg, H. and Blomgren, K. (2005) The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia. Cell Death Differ. 12, 162-176.   DOI
42 Zhu, Z., Yang, C., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S. G., Liu, J., Wang, Z., Tong, B. C., Song, J., Lu, J., Cheung, K. H. and Li, M. (2019) Balancing mTOR signaling and autophagy in the treatment of Parkinson's disease. Int. J. Mol. Sci. 20, 728.   DOI
43 Zolkipli-Cunningham, Z. and Falk, M. J. (2017) Clinical effects of chemical exposures on mitochondrial function. Toxicology 391, 90-99.   DOI
44 Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B. and Yuan, J. (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 281, 14474-14485.   DOI
45 Evans, C. S. and Holzbaur, E. L. F. (2020) Quality control in neurons: mitophagy and other selective autophagy mechanisms. J. Mol. Biol. 432, 240-260.   DOI
46 Grumati, P., Dikic, I. and Stolz, A. (2018) ER-phagy at a glance. J. Cell Sci. 131, jcs217364.   DOI
47 Adhami, F., Liao, G., Morozov, Y. M., Schloemer, A., Schmithorst, V. J., Lorenz, J. N., Dunn, R. S., Vorhees, C. V., Wills-Karp, M., Degen, J. L., Davis, R. J., Mizushima, N., Rakic, P., Dardzinski, B. J., Holland, S. K., Sharp, F. R. and Kuan, C. Y. (2006) Cerebral ischemiahypoxia induces intravascular coagulation and autophagy. Am. J. Pathol. 169, 566-583.   DOI
48 Vanhauwaert, R., Kuenen, S., Masius, R., Bademosi, A., Manetsberger, J., Schoovaerts, N., Bounti, L., Gontcharenko, S., Swerts, J., Vilain, S., Picillo, M., Barone, P., Munshi, S. T., de Vrij, F. M., Kushner, S. A., Gounko, N. V., Mandemakers, W., Bonifati, V., Meunier, F. A., Soukup, S. F. and Verstreken, P. (2017) The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals. EMBO J. 36, 1392-1411.   DOI
49 Wang, T., Martin, S., Papadopulos, A., Harper, C. B., Mavlyutov, T. A., Niranjan, D., Glass, N. R., Cooper-White, J. J., Sibarita, J. B., Choquet, D., Davletov, B. and Meunier, F. A. (2015b) Control of autophagosome axonal retrograde flux by presynaptic activity unveiled using botulinum neurotoxin type A. J. Neurosci. 35, 6179-6194.   DOI
50 Ohba, C., Nabatame, S., Iijima, Y., Nishiyama, K., Tsurusaki, Y., Nakashima, M., Miyake, N., Tanaka, F., Ozono, K., Saitsu, H. and Matsumoto, N. (2014) De novo WDR45 mutation in a patient showing clinically Rett syndrome with childhood iron deposition in brain. J. Hum. Genet. 59, 292-295.   DOI
51 Azarnia Tehran, D., Kuijpers, M. and Haucke, V. (2018) Presynaptic endocytic factors in autophagy and neurodegeneration. Curr. Opin. Neurobiol. 48, 153-159.   DOI
52 Alirezaei, M., Kemball, C. C., Flynn, C. T., Wood, M. R., Whitton, J. L. and Kiosses, W. B. (2010) Short-term fasting induces profound neuronal autophagy. Autophagy 6, 702-710.   DOI
53 Ariosa, A. R. and Klionsky, D. J. (2016) Autophagy core machinery: Overcoming spatial barriers in neurons. J. Mol. Med. 94, 1217-1227.   DOI
54 Ktistakis, N. T. and Tooze, S. A. (2016) Digesting the expanding mechanisms of autophagy. Trends Cell Biol. 26, 624-635.   DOI
55 Wurzer, B., Zaffagnini, G., Fracchiolla, D., Turco, E., Abert, C., Romanov, J. and Martens, S. (2015) Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. eLife 4, e08941.   DOI
56 Mazure, N. M. and Pouyssegur, J. (2010) Hypoxia-induced autophagy: cell death or cell survival? Curr. Opin. Cell Biol. 22, 177-180.   DOI
57 Mitra, S., Tsvetkov, A. S. and Finkbeiner, S. (2009) Protein turnover and inclusion body formation. Autophagy 5, 1037-1038.   DOI
58 Moore, A. S. and Holzbaur, E. L. (2016) Dynamic recruitment and activation of ALS-associated TBK1 with its target optineurin are required for efficient mitophagy. Proc. Natl. Acad. Sci. U.S.A. 113, E3349-E3358.
59 Ban, B. K., Jun, M. H., Ryu, H. H., Jang, D. J., Ahmad, S. T. and Lee, J. A. (2013) Autophagy negatively regulates early axon growth in cortical neurons. Mol. Cell. Biol. 33, 3907-3919.   DOI
60 Bar-Yosef, T., Damri, O. and Agam, G. (2019) Dual role of autophagy in diseases of the central nervous system. Front. Cell. Neurosci. 13, 196.   DOI
61 Son, J. H., Shim, J. H., Kim, K. H., Ha, J. Y. and Han, J. Y. (2012) Neuronal autophagy and neurodegenerative diseases. Exp. Mol. Med. 44, 89-98.   DOI
62 Tang, G., Gudsnuk, K., Kuo, S. H., Cotrina, M. L., Rosoklija, G., Sosunov, A., Sonders, M. S., Kanter, E., Castagna, C., Yamamoto, A., Yue, Z., Arancio, O., Peterson, B. S., Champagne, F., Dwork, A. J., Goldman, J. and Sulzer, D. (2014) Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron 83, 1131-1143.   DOI
63 Haack, T. B., Hogarth, P., Kruer, M. C., Gregory, A., Wieland, T., Schwarzmayr, T., Graf, E., Sanford, L., Meyer, E., Kara, E., Cuno, S. M., Harik, S. I., Dandu, V. H., Nardocci, N., Zorzi, G., Dunaway, T., Tarnopolsky, M., Skinner, S., Frucht, S., Hanspal, E., Schrander-Stumpel, C., Heron, D., Mignot, C., Garavaglia, B., Bhatia, K., Hardy, J., Strom, T. M., Boddaert, N., Houlden, H. H., Kurian, M. A., Meitinger, T., Prokisch, H. and Hayflick, S. J. (2012) Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. Am. J. Hum. Genet. 91, 1144-1149.   DOI
64 Hernandez, D., Torres, C. A., Setlik, W., Cebrian, C., Mosharov, E. V., Tang, G., Cheng, H. C., Kholodilov, N., Yarygina, O., Burke, R. E., Gershon, M. and Sulzer, D. (2012) Regulation of presynaptic neurotransmission by macroautophagy. Neuron 74, 277-284.   DOI
65 Hoffmann, S., Orlando, M., Andrzejak, E., Bruns, C., Trimbuch, T., Rosenmund, C., Garner, C. C. and Ackermann, F. (2019) LightActivated ROS production induces synaptic autophagy. J. Neurosci. 39, 2163-2183.   DOI
66 Joselin, A. P., Hewitt, S. J., Callaghan, S. M., Kim, R. H., Chung, Y. H., Mak, T. W., Shen, J., Slack, R. S. and Park, D. S. (2012) ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Hum. Mol. Genet. 21, 4888-4903.   DOI
67 Sheng, R. and Qin, Z. H. (2015) The divergent roles of autophagy in ischemia and preconditioning. Acta Pharmacol. Sin. 36, 411-420.   DOI
68 Smith, E. D., Prieto, G. A., Tong, L., Sears-Kraxberger, I., Rice, J. D., Steward, O. and Cotman, C. W. (2014) Rapamycin and interleukin1beta impair brain-derived neurotrophic factor-dependent neuron survival by modulating autophagy. J. Biol. Chem. 289, 20615-20629.   DOI
69 Kurth, I., Pamminger, T., Hennings, J. C., Soehendra, D., Huebner, A. K., Rotthier, A., Baets, J., Senderek, J., Topaloglu, H., Farrell, S. A., Nurnberg, G., Nurnberg, P., De Jonghe, P., Gal, A., Kaether, C., Timmerman, V. and Hubner, C. A. (2009) Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat. Genet. 41, 1179-1181.   DOI
70 Ramesh Babu, J., Lamar Seibenhener, M., Peng, J., Strom, A. L., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz-Meco, M. T., Moscat, J. and Wooten, M. W. (2008) Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration. J. Neurochem. 106, 107-120.   DOI
71 Rami, A., Langhagen, A. and Steiger, S. (2008) Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol. Dis. 29, 132-141.   DOI
72 Stavoe, A. K., Hill, S. E., Hall, D. H. and Colon-Ramos, D. A. (2016) KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses. Dev. Cell 38, 171-185.   DOI
73 Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M. Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J. H., Daumke, O. and Martens, S. (2019) FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol. Cell 74, 330-346.e11.   DOI
74 Van Laar, V. S., Roy, N., Liu, A., Rajprohat, S., Arnold, B., Dukes, A. A., Holbein, C. D. and Berman, S. B. (2015) Glutamate excitotoxicity in neurons triggers mitochondrial and endoplasmic reticulum accumulation of Parkin, and, in the presence of N-acetyl cysteine, mitophagy. Neurobiol. Dis. 74, 180-193.   DOI
75 Vijayan, V. and Verstreken, P. (2017) Autophagy in the presynaptic compartment in health and disease. J. Cell Biol. 216, 1895-1906.   DOI
76 Nikoletopoulou, V., Papandreou, M. E. and Tavernarakis, N. (2015) Autophagy in the physiology and pathology of the central nervous system. Cell Death Differ. 22, 398-407.   DOI
77 Nikoletopoulou, V., Sidiropoulou, K., Kallergi, E., Dalezios, Y. and Tavernarakis, N. (2017) Modulation of autophagy by BDNF underlies synaptic plasticity. Cell Metab. 26, 230-242.e5.   DOI
78 Philippidou, P., Valdez, G., Akmentin, W., Bowers, W. J., Federoff, H. J. and Halegoua, S. (2011) Trk retrograde signaling requires persistent, Pincher-directed endosomes. Proc. Natl. Acad. Sci. U.S.A. 108, 852-857.   DOI
79 Saito, T. and Sadoshima, J. (2015) Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circ. Res. 116, 1477-1490.   DOI
80 Shehata, M., Matsumura, H., Okubo-Suzuki, R., Ohkawa, N. and Inokuchi, K. (2012) Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression. J. Neurosci. 32, 10413-10422.   DOI
81 Tsvetkov, A. S., Miller, J., Arrasate, M., Wong, J. S., Pleiss, M. A. and Finkbeiner, S. (2010) A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc. Natl. Acad. Sci. U.S.A. 107, 16982-16987.   DOI
82 Stephan, A. H., Barres, B. A. and Stevens, B. (2012) The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35, 369-389.   DOI
83 Suzuki, K., Kubota, Y., Sekito, T. and Ohsumi, Y. (2007) Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12, 209-218.   DOI
84 Tsuyuki, S., Takabayashi, M., Kawazu, M., Kudo, K., Watanabe, A., Nagata, Y., Kusama, Y. and Yoshida, K. (2014) Detection of WIPI1 mRNA as an indicator of autophagosome formation. Autophagy 10, 497-513.   DOI
85 Soukup, S. F., Kuenen, S., Vanhauwaert, R., Manetsberger, J., Hernandez-Diaz, S., Swerts, J., Schoovaerts, N., Vilain, S., Gounko, N. V., Vints, K., Geens, A., De Strooper, B. and Verstreken, P. (2016) A LRRK2-dependent endophilinA phosphoswitch is critical for macroautophagy at presynaptic terminals. Neuron 92, 829-844.   DOI
86 Corrochano, S., Renna, M., Tomas-Zapico, C., Brown, S. D., Lucas, J. J., Rubinsztein, D. C. and Acevedo-Arozena, A. (2012) α-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington's disease pathology. Autophagy 8, 431-432.   DOI
87 Wallings, R. L., Humble, S. W., Ward, M. E. and Wade-Martins, R. (2019) Lysosomal dysfunction at the centre of parkinson's disease and frontotemporal dementia/amyotrophic lateral sclerosis. Trends Neurosci. 42, 899-912.   DOI
88 Wan, H., Wang, Q., Chen, X., Zeng, Q., Shao, Y., Fang, H., Liao, X., Li, H. S., Liu, M. G., Xu, T. L., Diao, M., Li, D., Meng, B., Tang, B., Zhang, Z. and Liao, L. (2020) WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death. Autophagy 16, 531-547.   DOI
89 Song, A. H., Wang, D., Chen, G., Li, Y., Luo, J., Duan, S. and Poo, M. M. (2009) A selective filter for cytoplasmic transport at the axon initial segment. Cell 136, 1148-1160.   DOI
90 Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H. and Nixon, R. A. (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J. Neurosci. 28, 6926-6937.   DOI
91 Ginet, V., Puyal, J., Clarke, P. G. and Truttmann, A. C. (2009) Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms. Am. J. Pathol. 175, 1962-1974.   DOI
92 Nicholls, D. G. and Budd, S. L. (2000) Mitochondria and neuronal survival. Physiol. Rev. 80, 315-360.   DOI
93 Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A. and Cuervo, A. M. (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol. 64, 113-122.   DOI
94 Okerlund, N. D., Schneider, K., Leal-Ortiz, S., Montenegro-Venegas, C., Kim, S. A., Garner, L. C., Waites, C. L., Gundelfinger, E. D., Reimer, R. J. and Garner, C. C. (2017) Bassoon controls presynaptic autophagy through Atg5. Neuron 93, 897-913.e7.   DOI
95 Liang, Y. and Sigrist, S. (2018) Autophagy and proteostasis in the control of synapse aging and disease. Curr. Opin. Nuerobiol. 48, 113-121.   DOI
96 Falcon, B., Noad, J., McMahon, H., Randow, F. and Goedert, M. (2018) Galectin-8-mediated selective autophagy protects against seeded tau aggregation. J. Biol. Chem. 293, 2438-2451.   DOI
97 Farfel-Becker, T., Roney, J. C., Cheng, X. T., Li, S., Cuddy, S. R. and Sheng, Z. H. (2019) Neuronal soma-derived degradative lysosomes are continuously delivered to distal axons to maintain local degradation capacity. Cell Rep. 28, 51-64.e4.   DOI
98 Luningschror, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C. R., Karl, F., Damme, M., Horowitz, A., Maystadt, I., Fuchtbauer, A., Fuchtbauer, E. M., Jablonka, S., Blum, R., Uceyler, N., Petri, S., Kaltschmidt, B., Jahn, R., Kaltschmidt, C. and Sendtner, M. (2017) Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nat. Commun. 8, 678.   DOI
99 Fox, J. H., Connor, T., Chopra, V., Dorsey, K., Kama, J. A., Bleckmann, D., Betschart, C., Hoyer, D., Frentzel, S., Difiglia, M., Paganetti, P. and Hersch, S. M. (2010) The mTOR kinase inhibitor everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease. Mol. Neurodegener. 5, 26.   DOI
100 Furuta, N., Fujita, N., Noda, T., Yoshimori, T. and Amano, A. (2010) Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol. Biol. Cell 21, 1001-1010.   DOI
101 Goo, M. S., Sancho, L., Slepak, N., Boassa, D., Deerinck, T. J., Ellisman, M. H., Bloodgood, B. L. and Patrick, G. N. (2017) Activity-dependent trafficking of lysosomes in dendrites and dendritic spines. J. Cell Biol. 216, 2499-2513.   DOI
102 Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E. and Zukin, R. S. (2010) Dysregulation of mTOR signaling in fragile X syndrome. J. Neurosci. 30, 694-702.   DOI
103 Reichardt, L. F. (2006) Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1545-1564.   DOI
104 Richter, B., Sliter, D. A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S. A., Youle, R. J. and Dikic, I. (2016) Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc. Natl. Acad. Sci. U.S.A. 113, 4039-4044.   DOI
105 Schwarz, L. A., Hall, B. J. and Patrick, G. N. (2010) Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway. J. Neurosci. 30, 16718-16729.   DOI
106 Shen, W. and Ganetzky, B. (2009) Autophagy promotes synapse development in Drosophila. J. Cell Biol. 187, 71-79.   DOI
107 Hill, S. E. and Colon-Ramos, D. A. (2020) The journey of the synaptic autophagosome: a cell biological perspective. Neuron 105, 961-973.   DOI
108 Koike, M., Shibata, M., Tadakoshi, M., Gotoh, K., Komatsu, M., Waguri, S., Kawahara, N., Kuida, K., Nagata, S., Kominami, E., Tanaka, K. and Uchiyama, Y. (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am. J. Pathol. 172, 454-469.   DOI
109 Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., Endo, T., Fon, E. A., Trempe, J. F., Saeki, Y., Tanaka, K. and Matsuda, N. (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510, 162-166.   DOI
110 Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H. and Mizushima, N. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889.   DOI
111 Benito-Cuesta, I., Diez, H., Ordonez, L. and Wandosell, F. (2017) Assessment of autophagy in neurons and brain tissue. Cells 6, 25.   DOI
112 Puyal, J., Vaslin, A., Mottier, V. and Clarke, P. G. (2009) Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann. Neurol. 66, 378-389.   DOI
113 Watanabe, S., Mamer, L. E., Raychaudhuri, S., Luvsanjav, D., Eisen, J., Trimbuch, T., Sohl-Kielczynski, B., Fenske, P., Milosevic, I., Rosenmund, C. and Jorgensen, E. M. (2018) Synaptojanin and endophilin mediate neck formation during ultrafast endocytosis. Neuron 98, 1184-1197.e6.   DOI
114 Kulkarni, A., Chen, J. and Maday, S. (2018) Neuronal autophagy and intercellular regulation of homeostasis in the brain. Curr. Opin. Nuerobiol. 51, 29-36.   DOI
115 Anding, A. L. and Baehrecke, E. H. (2017) Cleaning house: selective autophagy of organelles. Dev. Cell 41, 10-22.   DOI
116 Bailly, Y. (2013) Autophagy - A Double-Edged Sword: Cell Survival or Death? IntechOpen, London.
117 Briz, V., Hsu, Y. T., Li, Y., Lee, E., Bi, X. and Baudry, M. (2013) Calpain2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis. J. Neurosci. 33, 4317-4328.   DOI
118 Kulkarni, V. V. and Maday, S. (2018) Neuronal endosomes to lysosomes: a journey to the soma. J. Cell Biol. 217, 2977-2979.   DOI
119 Kurashige, T., Kuramochi, M., Ohsawa, R., Yamashita, Y., Shioi, G., Morino, H., Kamada, M., Ayaki, T., Ito, H., Sotomaru, Y., Maruyama, H. and Kawakami, H. (2020) Optineurin defects cause TDP43-pathology with autophagic vacuolar formation. Neurobiol. Dis. 148, 105215.
120 Bhaskara, R. M., Grumati, P., Garcia-Pardo, J., Kalayil, S., Covarrubias-Pinto, A., Chen, W., Kudryashev, M., Dikic, I. and Hummer, G. (2019) Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy. Nat. Commun. 10, 2370.   DOI
121 Carmona-Gutierrez, D., Hughes, A. L., Madeo, F. and Ruckenstuhl, C. (2016) The crucial impact of lysosomes in aging and longevity. Ageing Res. Rev. 32, 2-12.   DOI
122 Maiuri, M. C., Zalckvar, E., Kimchi, A. and Kroemer, G. (2007) Selfeating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8, 741-752.   DOI
123 Lee, K. M., Hwang, S. K. and Lee, J. A. (2013) Neuronal autophagy and neurodevelopmental disorders. Exp. Neurobiol. 22, 133-142.   DOI
124 Lee, S., Sato, Y. and Nixon, R. A. (2011) Primary lysosomal dysfunction causes cargo-specific deficits of axonal transport leading to Alzheimer-like neuritic dystrophy. Autophagy 7, 1562-1563.   DOI
125 Lim, J., Kim, H. W., Youdim, M. B., Rhyu, I. J., Choe, K. M. and Oh, Y. J. (2011) Binding preference of p62 towards LC3-ll during dopaminergic neurotoxin-induced impairment of autophagic flux. Autophagy 7, 51-60.   DOI
126 Wang, D. B., Kinoshita, Y., Kinoshita, C., Uo, T., Sopher, B. L., Cudaback, E., Keene, C. D., Bilousova, T., Gylys, K., Case, A., Jayadev, S., Wang, H. G., Garden, G. A. and Morrison, R. S. (2015a) Loss of endophilin-B1 exacerbates Alzheimer's disease pathology. Brain 138, 2005-2019.   DOI
127 Wang, M. M., Feng, Y. S., Yang, S. D., Xing, Y., Zhang, J., Dong, F. and Zhang, F. (2019) The relationship between autophagy and brain plasticity in neurological diseases. Front. Cell. Neurosci. 13, 228.   DOI
128 Williams, A., Jahreiss, L., Sarkar, S., Saiki, S., Menzies, F. M., Ravikumar, B. and Rubinsztein, D. C. (2006) Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr. Top. Dev. Biol. 76, 89-101.   DOI
129 Wen, Y. D., Sheng, R., Zhang, L. S., Han, R., Zhang, X., Zhang, X. D., Han, F., Fukunaga, K. and Qin, Z. H. (2008) Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4, 762-769.   DOI
130 Wild, P., McEwan, D. G. and Dikic, I. (2014) The LC3 interactome at a glance. J. Cell Sci. 127, 3-9.   DOI
131 Winden, K. D., Ebrahimi-Fakhari, D. and Sahin, M. (2018) Abnormal mTOR activation in autism. Annu. Rev. Neurosci. 41, 1-23.   DOI
132 Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., McCluskey, L. F., Miller, B. L., Masliah, E., Mackenzie, I. R., Feldman, H., Feiden, W., Kretzschmar, H. A., Trojanowski, J. Q. and Lee, V. M. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133.   DOI
133 Lee, S. H., Simonetta, A. and Sheng, M. (2004) Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron 43, 221-236.   DOI
134 Loeffler, D. A. (2019) Influence of normal aging on brain autophagy: a complex scenario. Front. Aging Neurosci. 11, 49.   DOI
135 Maday, S. and Holzbaur, E. L. (2014) Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway. Dev. Cell 30, 71-85.   DOI