Sex and gender differences in the molecular etiology of Parkinson's disease: considerations for study design and data analysis.

IF 4.9 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Biology of Sex Differences Pub Date : 2025-02-03 DOI:10.1186/s13293-025-00692-w

Samantha L Schaffner, Kira N Tosefsky, Amy M Inskter, Silke Appel-Cresswell, Julia M Schulze-Hentrich

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Abstract

Parkinson's disease (PD) is more prevalent in men than women, and presents with different clinical features in each sex. Despite widespread recognition of these differences, females are under-represented in clinical and experimental studies of PD, and much remains to be elucidated regarding the biological underpinnings of sex differences in PD. In this review, we summarize known contributors to sex differences in PD etiology across the life course, with a focus on neurological development and gene regulation. Sex differences that are established at conception and heightened during adolescence and midlife may partially embed future PD risk, due to the complex interactions between gonadal hormones, gene regulation, lifestyle factors, and aging. While the neuroprotective properties of estrogen are strongly implicated in reduced prevalence of PD in women, interactions with genotype and gender-biased lifestyle factors are incompletely understood. Consideration of sex and gender-related factors in study design, data analysis, and interpretation have the power to expedite our knowledge of the etiology of PD in men and in women, and to inform prevention and therapeutic strategies tailored to each sex.

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帕金森病分子病因学中的性别差异：研究设计和数据分析的考虑

帕金森病（PD）在男性中比女性更普遍，并且在两性中表现出不同的临床特征。尽管人们普遍认识到这些差异，但女性在帕金森病的临床和实验研究中代表性不足，关于帕金森病性别差异的生物学基础仍有待阐明。在这篇综述中，我们总结了在整个生命过程中导致PD病因性别差异的已知因素，重点是神经发育和基因调控。由于性腺激素、基因调控、生活方式因素和衰老之间复杂的相互作用，在怀孕时建立并在青春期和中年时期加强的性别差异可能部分嵌入未来PD风险。虽然雌激素的神经保护特性与降低女性PD患病率密切相关，但与基因型和性别偏见的生活方式因素的相互作用尚不完全清楚。在研究设计、数据分析和解释中考虑性别和与性别相关的因素，有能力加快我们对男性和女性PD病因的了解，并为针对每种性别的预防和治疗策略提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY

CiteScore

12.10

自引率

1.30%

发文量

审稿时长

14 weeks

期刊介绍： Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.