Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer’s disease

• Published in: BMB reports Vol. 57; no. 6; pp. 281 - 286
• Main 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
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 30-06-2024
• Subjects: Adult hippocampal neurogenesis; Bioinformatics; Hippocampal neural stem cell; microRNA; Mitochondria; Neurodegenerative disease; Hippocampal neural stem cell; microRNA; Neurodegenerative disease; Mitochondria; Bioinformatics; Adult hippocampal neurogenesis
• ISSN: 1976-6696; 1976-670X

Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. 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. 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. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer’s disease (AD). 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 novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD. [BMB Reports 2024; 57(6): 281-286]