97182 20210902121905.0 doi 10.3390/ijms21218043 sideral 121094 ART-2020-121094 eng Gracia, P. Universidad de Zaragoza Multiplicity of a-synuclein aggregated species and their possible roles in disease 2020 Access copy available to the general public Unrestricted a-Synuclein amyloid aggregation is a defining molecular feature of Parkinson’s disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer’s disease. The process of a-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of a-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of a-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct a-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases. info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100 info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-64119-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.923 2020 BIOCHEMISTRY & MOLECULAR BIOLOGY 67 / 297 = 0.226 2020 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 49 / 178 = 0.275 2020 Q2 T1 1.455 2020 Catalysis 2020 Q1 Computer Science Applications 2020 Q1 Inorganic Chemistry 2020 Q1 Spectroscopy 2020 Q1 Molecular Biology 2020 Q1 Organic Chemistry 2020 Q1 Physical and Theoretical Chemistry 2020 Q1 Medicine (miscellaneous) 2020 Q1 info:eu-repo/semantics/review info:eu-repo/semantics/publishedVersion (orcid)0000-0002-7848-5373 Camino, J.D. Universidad de Zaragoza Volpicelli-Daley, L. (orcid)0000-0002-9138-6687 Cremades, N. Universidad de Zaragoza 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 21, 21 (2020), 8043 [21 pp] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 501262 http://zaguan.unizar.es/record/97182/files/texto_completo.pdf Versión publicada 493485 http://zaguan.unizar.es/record/97182/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:97182 articulos driver 2021-09-02-10:39:01 ARTICLE