Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies; 35244787

Cascella, R. ; Bigi, A. ; Cremades, N. (Universidad de Zaragoza) ; Cecchi, C.

Resumen: Protein misfolding is a general hallmark of protein deposition diseases, such as Alzheimer’s disease or Parkinson’s disease, in which different types of aggregated species (oligomers, protofibrils and fibrils) are generated by the cells. Despite widespread interest, the relationship between oligomers and fibrils in the aggregation process and spreading remains elusive. A large variety of experimental evidences supported the idea that soluble oligomeric species of different proteins might be more toxic than the larger fibrillar forms. Furthermore, the lack of correlation between the presence of the typical pathological inclusions and disease sustained this debate. However, recent data show that the ß-sheet core of the a-Synuclein (aSyn) fibrils is unable to establish persistent interactions with the lipid bilayers, but they can release oligomeric species responsible for an immediate dysfunction of the recipient neurons. Reversibly, such oligomeric species could also contribute to pathogenesis via neuron-to-neuron spreading by their direct cell-to-cell transfer or by generating new fibrils, following their neuronal uptake. In this Review, we discuss the various mechanisms of cellular dysfunction caused by aSyn, including oligomer toxicity, fibril toxicity and fibril spreading. © 2022, The Author(s).

Idioma: Inglés

DOI: 10.1007/s00018-022-04166-9

Año: 2022

Publicado en: Cellular and Molecular Life Sciences 79, 3 (2022), 174 [20 pp]
ISSN: 1420-682X

Factor impacto JCR: 8.0 (2022)

Categ. JCR: CELL BIOLOGY rank: 36 / 191 = 0.188 (2022) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 36 / 285 = 0.126 (2022) - Q1 - T1

Factor impacto CITESCORE: 12.8 - Biochemistry, Genetics and Molecular Biology (Q1) - Neuroscience (Q1) - Pharmacology, Toxicology and Pharmaceutics (Q1)

Factor impacto SCIMAGO: 2.371 - Cell Biology (Q1) - Cellular and Molecular Neuroscience (Q1) - Pharmacology (Q1) - Molecular Medicine (Q1) - Molecular Biology (Q1)

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

Tipo y forma: Artículo (Versión definitiva)

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