Streptozotocin induces Alzheimer’s disease-like pathology in hippocampal neuronal cells via CDK5/Drp1-mediated mitochondrial fragmentation = 해마 신경세포주에 STZ 투여시 유도되는 알츠하이머병 관련 병태는 CDK5/Drp1 경로를 통한 미토콘드리아의 분절화 현상과 관련이 있음

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Title
Streptozotocin induces Alzheimer’s disease-like pathology in hippocampal neuronal cells via CDK5/Drp1-mediated mitochondrial fragmentation = 해마 신경세포주에 STZ 투여시 유도되는 알츠하이머병 관련 병태는 CDK5/Drp1 경로를 통한 미토콘드리아의 분절화 현상과 관련이 있음
Author(s)
Junghyung Park; Jinyoung Won; Jincheol Seo; Hyeon-Gu Yeo; Keonwoo Kim; Yu Gyeong Kim; Chang Yeop Jeon; M K Kam; Young-Hyun KimJae Won Huh; Sang-Rae Lee; D S Lee; Youngjeon Lee
Bibliographic Citation
Frontiers in Cellular Neuroscience, vol. 14, pp. 235-235
Publication Year
2020
Abstract
Aberrant brain insulin signaling plays a critical role in the pathology of Alzheimer’s disease (AD). Mitochondrial dysfunction plays a role in the progression of AD, with excessive mitochondrial fission in the hippocampus being one of the pathological mechanisms of AD. However, the molecular mechanisms underlying the progression of AD and mitochondrial fragmentation induced by aberrant brain insulin signaling in the hippocampal neurons are poorly understood. Therefore, we investigated the molecular mechanistic signaling associated with mitochondrial dynamics using streptozotocin (STZ), a diabetogenic compound, in the hippocampus cell line, HT-22 cells. In this metabolic dysfunctional cellular model, hallmarks of AD such as neuronal apoptosis, synaptic loss, and tau hyper-phosphorylation are induced by STZ. We found that in the mitochondrial fission protein Drp1, phosphorylation is increased in STZ-treated HT-22 cells. We also determined that inhibition of mitochondrial fragmentation suppresses STZ-induced AD-like pathology. Furthermore, we found that phosphorylation of Drp1 was induced by CDK5, and inhibition of CDK5 suppresses STZ-induced mitochondrial fragmentation and AD-like pathology. Therefore, these findings indicate that mitochondrial morphology and functional regulation may be a strategy of potential therapeutic for treating abnormal metabolic functions associated with the pathogenesis of AD.
Keyword
Alzheimer’s disease (AD)streptozotocin (STZ)hippocampusmitochondrial dynamicsdynamin-1-like protein (Drp1)cyclin-dependent kinase 5 (CDK5)
ISSN
1662-5102
Publisher
Frontiers Media Sa
DOI
http://dx.doi.org/10.3389/fncel.2020.00235
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
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