Decoding COPD-related cognitive impairment: The protective potential of YTHDF1.

Cognitive impairment is a significant complication in individuals with chronic obstructive pulmonary disease (COPD), which presents a substantial challenge to future healthcare resource allocation. However, the underlying therapeutic targets and mechanisms remain inadequately understood. In a study involving mice with COPD, hippocampal damage and deficits in working memory, spatial learning, and memory capabilities were observed following prolonged exposure to cigarette smoke (CS). CS exposure was found to induce apoptosis in hippocampal cells in vivo. Western blot and RT-qPCR analyses demonstrated a marked reduction in the expression of the m6A RNA-binding protein YTHDF1 compared to the control group. In vitro experiments related to the brain damage mechanism of COPD demonstrated a significant decrease in the level of YTHDF1 under hypoxic conditions. Notably, the overexpression of YTHDF1 mitigated hypoxia-induced apoptosis in HT22 cells. Furthermore, the overexpression of YTHDF1 attenuated cognitive impairment by reducing hippocampal neuronal apoptosis induced by CS. The findings suggest that YTHDF1 could have a substantial impact on cognitive dysfunction induced by COPD. Hypoxic conditions within hippocampal tissue may significantly contribute to this process, offering novel insights into the molecular mechanisms underlying COPD-related cognitive impairment.