Epigenetic Mechanisms Underlying Sex Differences in Neurodegenerative Diseases

Neurodegenerative diseases are complex disorders that, in most cases, arise from the interaction between genetic susceptibility and environmental risk factors. In this context, epigenetic mechanisms are crucial in neurodegenerative diseases’ pathogenesis, mediating environmental factors’ effects on proper genome functionality. Sex is an important variable in modulating the risk of developing neurodegenerative diseases and influences their clinical course. Although it is well established that epigenetic mechanisms are also influenced by sex, epigenetic differences between females and males affected by neurodegenerative diseases remain poorly investigated. This review summarizes the key evidence of sex-specific epigenetic alterations in major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Given the growing importance of gender medicine in the treatment of human diseases, a deeper understanding of sex-specific epigenetic mechanisms is highly relevant for neurodegenerative diseases.