Maf1 Loss Regulates Spinogenesis and Attenuates Cognitive Impairment in Alzheimer's Disease

Overview

Journal Brain

Publisher Oxford University Press

Specialty Neurology

Date 2024 Jan 16

PMID 38226680

Authors

Yingying Han

Kui Chen

Hongxiang Yu

Can Cui

Hongxia Li

Yongbo Hu

Bei Zhang

Gang Li

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease is neurodegenerative and characterized by progressive cognitive impairment. Synaptic dysfunction appears in the early stage of Alzheimer's disease and is significantly correlated with cognitive impairment. However, the specific regulatory mechanism remains unclear. Here, we found the transcription factor Maf1 to be upregulated in Alzheimer's disease and determined that conditional knockout of Maf1 in a transgenic mouse model of Alzheimer's disease restored learning and memory function; the downregulation of Maf1 reduced the intraneuronal calcium concentration and restored neuronal synaptic morphology. We also demonstrated that Maf1 regulated the expression of NMDAR1 by binding to the promoter region of Grin1, further regulating calcium homeostasis and synaptic remodelling in neurons. Our results clarify the important role and mechanism of the Maf1-NMDAR1 signalling pathway in stabilizing synaptic structure, neuronal function and behaviour during Alzheimer's disease pathogenesis. This therefore serves as a potential diagnostic and therapeutic target for the early stage of Alzheimer's disease.

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