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Comment
. 2023 Jul;39(7):1186-1188.
doi: 10.1007/s12264-023-01031-y. Epub 2023 Feb 4.

Linking Genetic Risks to Pathological α-Synuclein Transmission in Parkinson's Disease

Xiaoqing Mi  1 , Lei Chen  1 , Junxia Xie  2 , Ning Song  3
Affiliations
Comment

Linking Genetic Risks to Pathological α-Synuclein Transmission in Parkinson's Disease

Xiaoqing Mi et al. Neurosci Bull. 2023 Jul.
No abstract available

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Conflict of interest statement

All authors claim that there are no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Intercellularly-transmitted α-syn aggregates interact with cell surface receptors for internalization into neurons and glia. The membrane receptors GPNMB, LAG3, α3-NKA, PrPC, FcγRIIB, HSPG, TLR2, and Cx32 have been shown to interact with extracellular α-syn and facilitate its internalization into neurons. The internalized α-syn seeds the recruitment of endogenous α-syn aggregates, leading to pathological propagation. Glia also expresses membrane receptors responsible for α-syn internalization and thus trigger α-syn neurotoxicity. For example, PrPC, HSPG, and TLR2 have been reported on the cell surface of astrocytes, LAG3, PrPC, HSPG, and TLR2 on microglia, and HSPG and Cx32 on oligodendrocytes. GPNMB, glycoprotein non-metastatic melanoma protein B; LAG3, lymphocyte activation gene 3; α3-NKA, α3 subunit of the Na+/K+-ATPase complex; PrPC, cellular prion protein; HSPG, heparan sulfate proteoglycan; TLR2, toll-like receptor 2; Cx32, connexin-32; α-syn, α-synuclein.
See this image and copyright information in PMC

Comment on

  • GPNMB confers risk for Parkinson's disease through interaction with α-synuclein.
    Diaz-Ortiz ME, Seo Y, Posavi M, Carceles Cordon M, Clark E, Jain N, Charan R, Gallagher MD, Unger TL, Amari N, Skrinak RT, Davila-Rivera R, Brody EM, Han N, Zack R, Van Deerlin VM, Tropea TF, Luk KC, Lee EB, Weintraub D, Chen-Plotkin AS. Diaz-Ortiz ME, et al. Science. 2022 Aug 19;377(6608):eabk0637. doi: 10.1126/science.abk0637. Epub 2022 Aug 19. Science. 2022. PMID: 35981040 Free PMC article.

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