Streptozotocin Induces Alzheimer's Disease-Like Pathology in Hippocampal Neuronal Cells
Alzheimer’s disease (AD)
cyclin-dependent kinase 5 (CDK5)
dynamin-1-like protein (Drp1)
hippocampus
mitochondrial dynamics
streptozotocin (STZ)
Journal
Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935
Informations de publication
Date de publication:
2020
2020
Historique:
received:
27
04
2020
accepted:
02
07
2020
entrez:
9
9
2020
pubmed:
10
9
2020
medline:
10
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32903692
doi: 10.3389/fncel.2020.00235
pmc: PMC7438738
doi:
Types de publication
Journal Article
Langues
eng
Pagination
235Informations de copyright
Copyright © 2020 Park, Won, Seo, Yeo, Kim, Kim, Jeon, Kam, Kim, Huh, Lee, Lee and Lee.
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