Inflammatory factor A contributes to PD pathogenesis

摘要

Accumulating evidence suggests that aberrant brain insulin signaling plays a critical roles in the pathology of Alzheimer’s dis- ease (AD). Mitochondrial dysfunction is related to process of AD, with excessive mitochondrial fission in hippocampus being one of the pathological mechanisms of AD. However, the underlying molecular mechanisms between hippocampal neuronal loss and mitochondrial fragmentation induced by aberrant brain insulin signaling are poorly understood. Therefore, we investigated the molecular mechanistic signaling of mitochondrial dynamics in streptozotocin (STZ)-induced hippocampus cell line, HT-22 cells. We found that mitochondrial fission protein, Drp1 phosphorylation level is increased in STZ-treated HT-22 cells. We also determined inhibition of mitochondrial fragmentation suppressed STZ-induced neuronal loss. Furthermore, we found that Drp1 phosphorylation was effected by CDK5, and inhibition of CDK5 suppresses mitochon- drial fragmentation and neuronal loss. Therefore, we suggested that CDKS5 signal pathway is a key factor in the STZ-related neuronal death in AD through regulation of mitochondrial fragmentation.