Streptozotocin Induces Alzheimer’s Disease-Like Pathology in Hippocampal Neuronal Cells via CDK5/Drp1-Mediated Mitochondrial Fragmentation

Park, Junghyung and Won, Jinyoung and Seo, Jincheol and Yeo, Hyeon-Gu and Kim, Keonwoo and Kim, Yu Gyeong and Jeon, Chang-Yeop and Kam, Min Kyoung and Kim, Young-Hyun and Huh, Jae-Won and Lee, Sang-Rae and Lee, Dong-Seok and Lee, Youngjeon (2020) Streptozotocin Induces Alzheimer’s Disease-Like Pathology in Hippocampal Neuronal Cells via CDK5/Drp1-Mediated Mitochondrial Fragmentation. Frontiers in Cellular Neuroscience, 14. ISSN 1662-5102

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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.

Item Type: Article
Subjects: AP Academic Press > Medical Science
Depositing User: Unnamed user with email support@apacademicpress.com
Date Deposited: 22 May 2023 04:55
Last Modified: 15 Oct 2024 10:16
URI: http://info.openarchivespress.com/id/eprint/1340

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