• Molecules and Cells
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• 제38권5호
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• pp.381-389
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• 2015

Autophagy is a lysosome-dependent intracellular degradation process that allows recycling of cytoplasmic constituents into bioenergetic and biosynthetic materials for maintenance of homeostasis. Since the function of autophagy is particularly important in various stress conditions, perturbation of autophagy can lead to cellular dysfunction and diseases. Accumulation of abnormal protein aggregates, a common cause of neurodegenerative diseases, can be reduced through autophagic degradation. Recent studies have revealed defects in autophagy in most cases of neurodegenerative disorders. Moreover, deregulated excessive autophagy can also cause neurodegeneration. Thus, healthy activation of autophagy is essential for therapeutic approaches in neurodegenerative diseases and many autophagy-regulating compounds are under development for therapeutic purposes. This review describes the overall role of autophagy in neurodegeneration, focusing on various therapeutic strategies for modulating specific stages of autophagy and on the current status of drug development.

• BMB Reports
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• 제41권12호
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• pp.827-832
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• 2008

Many age-dependent neurodegenerative diseases are associated with the accumulation of abnormally folded proteins within neurons. One of the major proteolytic pathways in the cell is the autophagy pathway, which targets cytoplasmic contents and organelles to the lysosomes for bulk degradation under various physiological and stressful conditions. Although the importance of autophagy in cellular physiology is well appreciated, its precise roles in neurodegeneration remain largely unclear. Recent studies indicate that components of the endosomal sorting complex required for transport (ESCRT) are important in the autophagy pathway. Reduced activity of some ESCRT subunits leads to the accumulation of autophagosomes and failure to clear intracellular protein aggregates. Interestingly, rare mutations in CHMP2B, an ESCRT-III subunit, are associated with frontotemporal dementia linked to chromosome 3 (FTD3). Mutant CHMP2B proteins seem to disrupt the fusion of autophagosomes and lysosomes in cell culture models. These findings suggest a potential mechanism for the pathogenesis of FTD3 and possibly other neurodegenerative diseases as well.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.102.1-102.1
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• 2002

• Korean Journal of Radiology
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• 제25권2호
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• pp.214-215
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• 2024

• 대한한의학회지
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• 제25권4호
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• pp.95-107
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• 2004

Objective : The inappropriate or excessive apoptosis has been known to be associated with neurodegenerative disorders including intracranial hemorrhage(ICH). Paeoniae radix, in traditional Korean medicine, has played its role as blood­nourisher and yin-astringent. In the present study, the effect of Paeoniae radix on the inhibition of neurodegeneration in the brain of rats after artificial ICH and on the resulting apoptosis was investigated. Methods : 30 rats were divided into 6 equal groups ; the sham-operation group, the hemorrhage-induction group, the hemorrhage-induction with 10, 50, 100, and 200 mg/kg Paeoniae radix-treated group, respectively. Stereotactic surgery was performed and collagenase was infused to induce ICH in the region of CA1 of hippocampus of rats. The sham group took only saline infusion. For 7 days after the surgery, 4 testing groups had intraperitoneal injections of Paeoniae radix extract. The step-down inhibitory avoidance task, measurement of neurodegeneration degree in the CA1 region of the hippocampus, and detection of caspase-3 and newly generated cells in the dentate gyrus were done after animal sacrifice. Results : Rats receiving Paeoniae radix extract showed increased latency time in the inhibitory avoidance task. The extension of neuron-deprived areas in the CA1 region was significantly suppressed in the Paeonia treated groups. Also expressions of caspase-3 in the CA1 region and cortex were significantly inhibited in the Paeonia treated groups. The cell proliferation was evaluated by means of BrdU methods and proved to be decreased in the Paeonia treated groups. Conclusion : These results suggest that Paeoniae radix has potential to suppress short-tenn memory loss after devastating neurologic accidents. Also it was proved that Paeoniae radix has a neuroprotective effect and alleviates central nervous complications following intracerebral hemorrhage. Furthermore, it may imply that this medicinal plant can be widely used for vascular dementia and other neurodegenerative disorders.

• 한국발생생물학회지:발생과생식
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• 제13권2호
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• pp.63-77
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• 2009

신경리포푸신증(NCLs)은 신경퇴행 축적 질환으로 뇌에 자기형광물질을 포함한 다양한 물질의 축적이 야기되어 발생하며, 노던에필렙시를 제외한 모든 신경포푸신증은 리소즘 축적 질환으로 분류된다. 이러한 신경리포푸신증은 전세계적으로 12,500명 중 1명에게 발생되는 높은 발병 빈도를 나타내며, 그 발병 시기에 따라 영아형, 영유아형, 유년형, 그리고 성인형과 같이 분류된다. 신경리포푸신증이 유발하는 의학적 증상로는 시각 손실, 발작, 간질, 진행성 정신지체등을 야기하여 소아성 치매라는 이야기를 들으며, 증상이 심할 경우 환자가 사망에 이르게 된다. 신경퇴행성 리포푸신증의 원인은 유전자의 돌연변이 때문이라고 알려져 있으며, 일부의 연구를 통해 태아의 발생과정 상 문제를 통해 질병이 야기되는 경우도 관찰이 되고 있으나, 아직 그 분자 발생학적 기전이 명확하게 규명되어 있지 않은 현실이다. 현재 전 세계적으로 많은 연구가 수행되고 있어 그 결과가 주목되는 바이다.

• 한국응용과학기술학회지
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• 제37권4호
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• pp.762-768
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• 2020

This study aimed to investigate the effect of ladder-climbing exercise training on neurobiological markers in the hippocampus of mice with type 2 diabetes (T2DM). Twenty-one C57BL/6 male mice were randomly assigned to the non-diabetic control (NDC, n = 7), diabetic control (DC, n = 7), and diabetic training (DT, n = 7) groups. The DT group performed ladder-climbing training (LCT) five times a week for eight weeks. We measured the levels of hippocampal neurobiological markers (catalase [CAT], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], amyloid-beta [Aβ], tau, and CC motif chemokine ligand 11 [CCL11]). The BDNF levels were significantly higher in the DT group than in the DC group (p < 0.05). The Aβ and CCL11 levels were significantly higher in the DC group than in the NDC and DT groups (p < 0.05). The tau levels were significantly higher in the DC group than in the NDC group (p < 0.05). However, there was no significant difference in CAT and NGF levels among the groups (p > 0.05). These results suggest that while T2DM could induce neurodegeneration, LCT may be effective in alleviating neurodegeneration caused by T2DM.

• 대한약침학회지
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• 제26권4호
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• pp.327-337
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• 2023

Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.

• Clinical and Experimental Pediatrics
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• 제48권9호
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• pp.920-923
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• 2005

Epilepsy is a neurological disorder from many molecular and biochemical responses. In the underlying mechanism, free radicals play an important role in seizure initiation and seizure-induced brain damage. Excessive production of oxygen free radicals and other radical species have been implicated in the development of seizures under pathological conditions and linked to seizure-induced neurodegeneration.

• BMB Reports
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• 제47권8호
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• pp.424-432
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• 2014

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.