Impact of sex on neuroimmune contributions to Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Inflammation has been observed in both the idiopathic and familial forms of PD. Importantly, PD is reported more often in men than in women, men having at least 1.5- fold higher risk to develop PD than women. This review summarizes the impact of biological sex and sex hormones on the neuroimmune contributions to PD and its investigation in animal models of PD. Innate and peripheral immune systems participate in the brain neuroinflammation of PD patients and is reproduced in neurotoxin, genetic and & alpha;-synuclein based models of PD. Microglia and astrocytes are the main cells of the innate immune system in the central nervous system and are the first to react to restore homeostasis in the brain. Analysis of serum immunoprofiles in female and male control and PD patients show that a great proportion of these markers differ between males and females. The relationship between cerebrospinal fluid inflammatory markers and PD clinical characteristics or PD biomarkers shows sex differences. Conversely, in animal models of PD, sex differences in inflammation are well documented and the beneficial effects of endogenous and exogenous estrogenic modulation in inflammation have been reported. Targeting neuroinflammation in PD is an emerging therapeutic option but gonadal drugs have not yet been investigated in this respect, thus offering new opportunities for sex specific treatments.