Escape from X-chromosome inactivation and sex differences in Alzheimer’s disease
Author:
Song Qing-Hua1, Zhao Ke-Xuan1, Huang Shuai1, Chen Tong1, He Ling1
Affiliation:
1. Department of Pharmacology , China Pharmaceutical University , No. 24 Tong Jia Xiang , Nanjing 210009 , Jiangsu Province , China
Abstract
Abstract
Sex differences exist in the onset and progression of Alzheimer’s disease. Globally, women have a higher prevalence, while men with Alzheimer’s disease experience earlier mortality and more pronounced cognitive decline than women. The cause of sex differences in Alzheimer’s disease remains unclear. Accumulating evidence suggests the potential role of X-linked genetic factors in the sex difference of Alzheimer’s disease (AD). During embryogenesis, a remarkable process known as X-chromosome inactivation (XCI) occurs in females, leading to one of the X chromosomes undergoing transcriptional inactivation, which balances the effects of two X chromosomes in females. Nevertheless, certain genes exceptionally escape from XCI, which provides a basis for dual expression dosage of specific genes in females. Based on recent research findings, we explore key escape genes and their potential therapeutic use associated with Alzheimer’s disease. Also, we discuss their possible role in driving the sex differences in Alzheimer’s disease. This will provide new perspectives for precision medicine and gender-specific treatment of AD.
Funder
China Postdoctoral Science Foundation National Natural Science Foundation of China “Double First Class” University project
Publisher
Walter de Gruyter GmbH
Subject
General Neuroscience
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