Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (1): 377-391.doi: 10.4103/NRR.NRR-D-23-01511

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Chitosan alleviates symptoms of Parkinson’s disease by reducing acetate levels, which decreases inflammation and promotes repair of the intestinal barrier and blood– brain barrier

Yinying Wang1, 2, #, Rongsha Chen1, #, Guolin Shi3 , Xinwei Huang1 , Ke Li1 , Ruohua Wang1 , Xia Cao1 , Zhongshan Yang2, *, Ninghui Zhao3, *, Jinyuan Yan1, *   

  1. 1 Central Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China;  2 Yunnan Provincial Key Laboratory of Molecular Biology for Sino Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan Province, China;  3 Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
  • Online:2026-01-15 Published:2025-04-24
  • Contact: Zhongshan Yang, PhD, yangzhongshan@ynucm.edu.cn; Ninghui Zhao, MD, zhaoninghui@kmmu.edu.cn; Jinyuan Yan, PhD, yanjinyuan@kmmu.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY); a grant from Yunnan Department of Science and Technology, Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY).

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Abstract: Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson’s disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson’s disease.

Key words: acetate, adenosine 5′-monophosphate-activated protein kinase, blood–brain barrier, chitosan, dopamine neurons, inflammation, intestinal barrier, Parkinson’s disease, peroxisome proliferator-activated receptor delta, short-chain fatty acids