Sex Differences in Dopaminergic Vulnerability to Environmental Toxicants - Implications for Parkinson's Disease.
Sex Differences in Dopaminergic Vulnerability to Environmental Toxicants - Implications for Parkinson's Disease.
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DOI：
10.1007/s40572-022-00380-6
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发表时间：
2022-12
影响因子：
7.9
通讯作者：
De Miranda, Briana R.
中科院分区：
文献类型：
--
作者：
Adamson, Ashley;Buck, Silas A.;Freyberg, Zachary;De Miranda, Briana R.
帕金森病（PD）的性别二态性是神经系统疾病的一个表面特征，特别是男性患PD的可能性是女性的1.5-2倍。疾病的临床特征，如发病时的表现、最普遍的症状和对治疗的反应也受性别的影响。尽管这些众所周知的性别差异在PD的风险和表型，机制，赋予性别二态性在PD仍然知之甚少。由于PD发病率受环境因素的影响，最近在研究中出现了一种有趣的模式，表明男性特异性易受神经毒物暴露引起的多巴胺能神经变性的影响，女性则具有相对保护作用。这些新的实验数据揭示了潜在的机制，为多巴胺能神经变性和其他PD病理学（如α-突触核蛋白毒性）的性别差异来源提供了线索。在这篇综述中，我们讨论了新出现的证据表明，男性对环境暴露引起的神经退行性变的敏感性增加。我们研究了多巴胺能神经变性和PD相关病理的潜在机制，并有证据支持雌激素，SRY表达，囊泡谷氨酸转运蛋白VGLUT 2和微生物组作为男性脆弱性的潜在催化剂的作用。我们还强调了将性别作为生物学变量的重要性，特别是在PD背景下评估多巴胺能神经毒性时。
Sex dimorphism in Parkinson’s disease (PD) is an ostensible feature of the neurological disorder, particularly as men are 1.5-2 times more likely to develop PD than women. Clinical features of the disease, such as presentation at onset, most prevalent symptoms, and response to treatment are also affected by sex. Despite these well-known sex differences in PD risk and phenotype, the mechanisms that impart sex dimorphisms in PD remain poorly understood. As PD incidence is influenced by environmental factors, an intriguing pattern has recently emerged in research studies suggesting a male-specific vulnerability to dopaminergic neurodegeneration caused by neurotoxicant exposure, with relative protection in females. These new experimental data have uncovered potential mechanisms that provide clues to the source of sex differences in dopaminergic neurodegeneration and other PD pathology such as alpha-synuclein toxicity. In this review, we discuss the emerging evidence of increased male sensitivity to neurodegeneration from environmental exposures. We examine mechanisms underlying dopaminergic neurodegeneration and PD-related pathologies with evidence supporting the roles of estrogen, SRY expression, the vesicular glutamate transporter VGLUT2, and the microbiome as prospective catalysts for male vulnerability. We also highlight the importance of including sex as a biological variable, particularly when evaluating dopaminergic neurotoxicity in the context of PD.
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影响因子：
4.1
作者：
Caboni, P;Sherer, TB;Casida, JE
通讯作者：
Casida, JE
影响因子：
2.9
作者：
Arvin, M;Fedorkova, L;Leipheimer, RE
通讯作者：
Leipheimer, RE
雌激素和雌激素样分子在神经发生和神经变性中的影响：有益还是有害？
影响因子：
5.3
作者：
Bustamante-Barrientos FA;Méndez-Ruette M;Ortloff A;Luz-Crawford P;Rivera FJ;Figueroa CD;Molina L;Bátiz LF
通讯作者：
Bátiz LF
DOI：
10.1126/science.aam9080
发表时间：
2017-09-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burbulla LF;Song P;Mazzulli JR;Zampese E;Wong YC;Jeon S;Santos DP;Blanz J;Obermaier CD;Strojny C;Savas JN;Kiskinis E;Zhuang X;Krüger R;Surmeier DJ;Krainc D
通讯作者：
Krainc D
影响因子：
6.1
作者：
Chen, Honglei;Wang, Keran;Scheperjans, Filip;Killinger, Bryan
通讯作者：
Killinger, Bryan