| Autor: |
Li Sun, Wen-Wen Jiang, Ye Wang, Yong-Sheng Yuan, Zhe Rong, Jing Wu, Yi Fan, Ming Lu, Ke-Zhong Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell Death Discovery, Vol 7, Iss 1, Pp 1-10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-021-00676-w |
| Popis: |
Abstract To investigate the mechanism of peripheral neuropathy in Parkinson’s disease (PD), we prepared a PD mice model by long-term exposure of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic PD pathology in humans and the sciatic nerves were taken for further research. It turned out that phosphorylated α-synuclein (p-α-syn) was significantly deposited in Schwann cells (SCs) of sciatic nerves possibly contributing to degenerated myelin SCs and atrophied axons in MPTP group. Further analysis confirmed that toll-like receptors (TLRs) were implicated with PD peripheral neuropathy, in which TLR2 exhibits the predominant expression. Increased expression of inflammatory factors about TLR2/nuclear factor kappa-B (NF-κB) pathway was noted in MPTP group compared to saline group, with proteins on other pathways showing no changes. Moreover, MPTP-challenged mice exhibited worse motor ability and damaged nerve conduction, implicating that p-α-syn neurotoxicity might be relevant to impairments of motor and sensory nerves. After the treatment of CU-CPT22, a TLR2 antagonist, p-α-syn accumulation, motor and sensory function were ameliorated in CU-CPT22 combined with MPTP group. Thus, we demonstrated that pathological p-α-syn might combine TLR2 to affect SCs activation, inflammatory response as well as motor and sensory function through TLR2/nuclear factor kappa-B (NF-κB) signaling pathway. This study firstly demonstrates a novel mechanism of p-α-syn accumulated in SCs of peripheral nerves, which extends our understanding on SCs-mediated peripheral neuroinflammation related to TLR2/NF-κB signaling pathway and sheds light on potential new therapeutic avenues for PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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