The role of genetics and gender specific differences in neurodegenerative disorders: Insights from molecular and immune landscape.

Neurodegenerative disorders (NDDs) are the most common neurological disorders with high prevalence and have significant socioeconomic implications. Understanding the underlying cellular and molecular mechanisms associated with the immune system can be effective in disease etiology, leading to more effective therapeutic approaches for both females and males. The central nervous system (CNS) actively participates in immune responses, both within and outside the CNS. Immune system activation is a common feature in NDDs. Gender-specific factors play a significant role in the prevalence, progression, and manifestation of NDDs. Neuroinflammation, in both inflammatory neurological and neurodegenerative conditions, is defined by the triggering of microglia and astrocyte cell activation. This results in the secretion of pro-inflammatory cytokines and chemokines. Numerous studies have documented the role of neuroinflammation in neurological diseases, highlighting the involvement of immune signaling pathways in disease development. Converging evidence support immune system involvement during neurodegeneration in NDDs. In this review, we summarize emerging evidence that reveals gender-dependent differences in immune responses related to NDDs. Also, we highlight sex differences in immune responses and discuss how these sex-specific influences can increase the risk of NDDs. Understanding the role of gender-specific factors can aid in developing targeted therapeutic strategies and improving patient outcomes. Ultimately, the better understanding of these mechanisms contributed to sex-dependent immune response in NDDs, can be critically usful in targeting of immune signaling cascades in such disorders. In this regard, sex-related immune responses in NDDs may be promising and effective targets in therapeutic strategies.