Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia

Abstract

Epidemiological studies and clinical observations show evidence of sexual dimorphism in brain responses to several neurological conditions. It is suggested that sex-related differences between men and women may have profound effects on disease susceptibility, pathophysiology, and progression. Sexual differences of the brain are achieved through the complex interplay of several factors contributing to this phenomenon, such as sex hormones, as well as genetic and epigenetic differences. Despite recent advances, the precise link between these factors and brain disorders is incompletely understood. This review aims to briefly outline the most relevant aspects that differ between men and women in ischemia and neurodegenerative disorders (AD, PD, HD, ALS, and SM). Recognition of disparities between both sexes could aid the development of individual approaches to ameliorate or slow the progression of intractable disorders.

Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities

“…Epidemiological data show that the prevalence of AD differs between men and women, the latter having a higher risk and incidence of developing AD than men (approximately 2:1), with more progressive cognitive and physical decline [ 25 ]. Women and men also exhibit different clinical features, in terms of disease duration (longer in women) and concomitant neuropsychiatric disturbances.…”

“…In men, the loss of steroid hormones was less drastic. Even if the level of circulating testosterone exhibited a gradual decline over time, its reduced levels due to aging may also increase the occurrence of the disease in men [ 25 ]. Moreover, the reduction in estradiol levels during and beyond the fifth decade of life may be responsible for deficits of cerebral metabolism and vascular pathologies mainly among women, since males of the same age would continue to aromatize testosterone into estrogens [ 79 ].…”

“…In the sporadic forms of AD, the association of homozygous single nucleotide polymorphisms (SNP) of ESR1 and ESR2 with apolipoprotein E4 ( ApoE4 ) conferred an increased risk of cognitive impairment in both sexes, with a higher prevalence in women. Indeed, the research data points out that the risk of AD is even more pronounced in women carriers of the e4 allele of APOE than men [ 25 ].…”

Raspberry polyphenols alleviate neurodegenerative diseases: through gut microbiota and ROS signals

“…It protects cells from H 2 O 2 -induced oxidative stress and attenuate brain ischemic injury in animal models by engaging the NFR2 pathway and upregulating HO-1, 147 which may be useful for the treatment of Parkinson's disease and ALS. 148 5.2.3 MAPK pathway. Mitogen-activated protein kinases (MAPKs) are a class of transferases that regulate cellular life processes.…”

“…It protects cells from H 2 O 2 -induced oxidative stress and attenuate brain ischemic injury in animal models by engaging the NFR2 pathway and upregulating HO-1, 147 which may be useful for the treatment of Parkinson's disease and ALS. 148…”