Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer ’s disease
This study aims to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorder. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells, as an in vitro model for cognitive impairment. Remarkably, miR-150-3p, miR-323-5p, and miR-370-3p which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. Notably, these miRNAs collectively target the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Furthermore, data-driven analyses involving human subjects within the hippocampus and brain revealed significant reductions of OPA1 and MFN2 in the Alzheimer's disease (AD) patients. Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide a novel insight into the intricate connection between miRNAs and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.PMID:38053296
Source: BMB Reports - Category: Biochemistry Authors: A Reum Han Tae Kwon Moon Im Kyeung Kang Dae Bong Yu Yechan Kim Cheolhwan Byon Sujeong Park Hae Lin Kim Kyoung Jin Lee Heuiran Lee Ha-Na Woo Seong Who Kim Source Type: research