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REVIEW article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1470171
This article is part of the Research Topic Physiopathology of alpha-synuclein: a bench-to-bedside overview View all articles

Intercellular transmission of alpha-synuclein

Provisionally accepted
Shenjie Wu Shenjie Wu 1,2Randy W. Schekman Randy W. Schekman 1,2*
  • 1 University of California, Berkeley, Berkeley, United States
  • 2 Howard Hughes Medical Institute (HHMI), Chevy Chase, Maryland, United States

The final, formatted version of the article will be published soon.

    An emerging theme in Parkinson's disease (PD) is the propagation of α-synuclein pathology as the disease progresses. Research involving the injection of preformed αsynuclein fibrils (PFFs) in animal models has recapitulated the pathological spread observed in PD patients. At the cellular and molecular levels, this intercellular spread requires the translocation of α-synuclein across various membrane barriers. Recent studies have identified subcellular organelles and protein machineries that facilitate these processes. In this review, we discuss the proposed pathways for α-synuclein intercellular transmission, including unconventional secretion, receptor-mediated uptake, endosome escape and nanotube-mediated transfer. In addition, we advocate for a rigorous examination of the evidence for the localization of α-synuclein in extracellular vesicles.

    Keywords: alpha synuclein, Parkinson's disease, Braak hypothesis, Unconventional secretion, receptor-mediated uptake, Endosome Escape, Tunneling nanotube, Extracellular vesicle (EV)

    Received: 25 Jul 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Wu and Schekman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Randy W. Schekman, Howard Hughes Medical Institute (HHMI), Chevy Chase, 20815-6789, Maryland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.