2. Academic Validation
  3. Melatonin ameliorates Parkinson's disease via regulating microglia polarization in a RORα-dependent pathway

Melatonin ameliorates Parkinson's disease via regulating microglia polarization in a RORα-dependent pathway

  • NPJ Parkinsons Dis. 2022 Jul 8;8(1):90. doi: 10.1038/s41531-022-00352-5.
Jingwen Li  # 1,  Hanshu Liu  # 1,  Xinyi Wang 1,  Yun Xia 1,  Jinsha Huang 1,  Tao Wang 1,  Zhicheng Lin 2,  Nian Xiong 3
Affiliations

Affiliations

  • 1 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 2 Laboratory of Psychiatric Neurogenomics, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
  • 3 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. nianxiong@hust.edu.cn.
  • # Contributed equally.
PMID: 35803929 DOI: 10.1038/s41531-022-00352-5
Abstract

An important pathophysiological component of Parkinson's Disease (PD) is circadian rhythm disorder, closely related to a decrease in circulated melatonin (MLT) level. It has been reported recently that retinoic acid-associated orphan nuclear receptor (RORα), for the potentiallyendogenous ligand MLT, plays an important role in various diseases. However, the function of RORα in the pathogenesis of neurodegenerative diseases remains much unclear. Here, we showed in a cellular PD model that RORα expression was down-regulated in 1 methyl 4 phenyl pyridinium ion (MPP+)-treated BV2 cells but up-regulated by MLT. Of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - induced mouse model with RORα levels reduced in the midbrain tissue, MLT treatment (intraperitoneal 20 mg/kg/d for 7 days) significantly increased the RORα levels and protected dopamine neurons, with decreased inflammation and increased anti-inflammatory M2-like phenotype in the microglia. Furthermore, siRNA-mediated knockdown implied the involvement of signal transducer and activator of transcription (STAT) pathway. In conclusion, MLT ameliorates neuroinflammation by inhibiting STAT-related pro-inflammatory (M1-like) polarization of microglia, revealing alternative options for neuroprotective treatment of PD.

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