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Updated: Jun 9, 2025

Analyzing the Parkinson's Disease Mouse Model Induced by Adeno-associated Viral Vectors Encoding Human α-Synuclein
Published on: July 29, 2022
Bidirectional interaction between IL and 17A/IL-17RA pathway dysregulation and α-synuclein in the pathogenesis of
Yu-Chen Yan1, Lu Su1, Wan-Bing Zhao1
1Department of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Abstract:
Parkinson's disease (PD) pathogenesis is characterized by α-synuclein (α-syn) pathology, which is influenced by various factors such as neuroinflammation and senescence. Increasing evidence has suggested a pivotal role for Interleukin-17A(IL-17A) and Interleukin-17 Receptor A (IL-17RA) in PD, yet the trigger and impact of IL-17A/IL-17RA activation in PD remains elusive. This study observed an age-related increase in IL-17A and IL-17RA in the human central nervous system, accompanied by increased α-syn and senescence biomarkers. Interestingly, both levels of IL-17A and IL-17RA in PD patients were significantly elevated compared to age-matched controls, wherein the IL-17A was mainly present in neurons. This abnormal neuronal IL-17A activation in the PD brain was recapitulated in α-syn mouse models. Correspondingly, administration of recombinant IL-17A exacerbated pathological α-syn in both neuron and mouse models. Furthermore, IL-17A/IL-17RA pathway interventions via blocking antibody or shRNA-mediated knockdown can mitigate the effects of pathological α-syn. This study reveals an interplay between dysregulation of the IL-17A/IL-17RA pathway and α-syn, suggesting that regulating the IL-17A/IL-17RA pathway could modify PD progression by disrupting the detrimental cycle.
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