• Linfeng Zhou, Yun Li, Min Wang, Wenjing Han, Qiang Chen, Ji Zhang, Bo Sun, and Yi Fan.
• Neuroprotective Drug Discovery Center of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, Nanjing, PR China.
• Neuroscience. 2023 Jul 15; 523: 809080-90.

AbstractEpidemiological studies have demonstrated that women are less susceptible to Parkinson's disease (PD) than men. Estrogen exposure is hypothesized to confer protection against dopaminergic neuronal loss in patients with PD. Although the accumulation and propagation of α-synuclein (α-Syn) are closely linked to the clinical progression of PD, no relevant research has examined whether α-Syn proteostasis in the brain is altered in women after menopause. In this study, we established long-term ovariectomized (OVX) mice to simulate late post-menopause and investigated the expression and aggregation of α-Syn following the ovariectomy procedure. We observed that the OVX mice exhibited a significant increase in the expression and aggregation of α-Syn in the striatum and midbrain accompanied by impaired motor performance at 3 months after ovariectomy. The accumulation of α-Syn did not result in a significant loss of nigral dopaminergic neurons but did enhance autophagy and neuroglial activation. These findings imply that menopause may disrupt α-Syn proteostasis and exacerbate the accumulation of α-Syn in the basal ganglia circuit.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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