Mechanisms of alpha-synuclein toxicity: An update and outlook.
| Autor: | Brás IC; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany., Xylaki M; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany., Outeiro TF; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany; Max Planck Institute for Experimental Medicine, Göttingen, Germany; Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address: touteir@gwdg.de. |
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| Jazyk: | angličtina |
| Zdroj: | Progress in brain research [Prog Brain Res] 2020; Vol. 252, pp. 91-129. Date of Electronic Publication: 2019 Nov 23. |
| DOI: | 10.1016/bs.pbr.2019.10.005 |
| Abstrakt: | Alpha-synuclein (aSyn) was identified as the main component of inclusions that define synucleinopathies more than 20 years ago. Since then, aSyn has been extensively studied in an attempt to unravel its roles in both physiology and pathology. Today, studying the mechanisms of aSyn toxicity remains in the limelight, leading to the identification of novel pathways involved in pathogenesis. In this chapter, we address the molecular mechanisms involved in synucleinopathies, from aSyn misfolding and aggregation to the various cellular effects and pathologies associated. In particular, we review our current understanding of the mechanisms involved in the spreading of aSyn between different cells, from the periphery to the brain, and back. Finally, we also review recent studies on the contribution of inflammation and the gut microbiota to pathology in synucleinopathies. Despite significant advances in our understanding of the molecular mechanisms involved, we still lack an integrated understanding of the pathways leading to neurodegeneration in PD and other synucleinopathies, compromising our ability to develop novel therapeutic strategies. (© 2020 Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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