Multiplicity of a-synuclein aggregated species and their possible roles in disease

Gracia, P. (Universidad de Zaragoza) ; Camino, J.D. (Universidad de Zaragoza) ; Volpicelli-Daley, L. ; Cremades, N. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/ijms21218043

Año: 2020

Publicado en: International Journal of Molecular Sciences 21, 21 (2020), 8043 [21 pp]
ISSN: 1661-6596

Factor impacto JCR: 5.923 (2020)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 67 / 297 = 0.226 (2020) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 49 / 178 = 0.275 (2020) - Q2 - T1

Factor impacto SCIMAGO: 1.455 - Catalysis (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Molecular Biology (Q1) - Organic Chemistry (Q1) - Physical and Theoretical Chemistry (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MCIU-FEDER/PGC2018-096335-B-100
Financiación: info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-64119-P

Tipo y forma: Review (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)