Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2020.00235
Keywords
Alzheimer's disease (AD); streptozotocin (STZ); hippocampus; mitochondrial dynamics; dynamin-1-like protein (Drp1); cyclin-dependent kinase 5 (CDK5)
Categories
Funding
- Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program [KGM5282022, KGM4622013, KGC1022012]
- National Research Council of Science & Technology (NST), Republic of Korea [KGM4622013, KGC1022012, KGM5282022] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available