中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (11): 2332-2342.doi: 10.4103/1673-5374.371345

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

α-突触核蛋白低聚物和原纤维:突触核蛋白疾病中的犯罪伙伴

  

  • 出版日期:2023-11-15 发布日期:2023-05-04

α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies

Alessandra Bigi, Roberta Cascella, Cristina Cecchi*   

  1. Department of Experimental and Clinical Biomedical Sciences, Section of Biochemistry, University of Florence, Florence, Italy
  • Online:2023-11-15 Published:2023-05-04
  • Contact: Cristina Cecchi, PhD, cristina.cecchi@unifi.it.
  • Supported by:
    The work was supported by the University of Florence (Fondi Ateneo to RC and CC), and the Ministry of Education, Universities and Research of Italy (Progetto Dipartimento di Eccellenza to CC).

摘要: https://orcid.org/0000-0002-1067-6288 (Alessandra Bigi); https://orcid.org/0000-0001-9856-6843 (Roberta Cascella); https://orcid.org/0000-0001-8387-7737 (Cristina Cecchi) 

Abstract: The misfolding and aggregation of α-synuclein is the general hallmark of a group of devastating neurodegenerative pathologies referred to as synucleinopathies, such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. In such conditions, a range of different misfolded aggregates, including oligomers, protofibrils, and fibrils, are present both in neurons and glial cells. Growing experimental evidence supports the proposition that soluble oligomeric assemblies, formed during the early phases of the aggregation process, are the major culprits of neuronal toxicity; at the same time, fibrillar conformers appear to be the most efficient at propagating among interconnected neurons, thus contributing to the spreading of α-synuclein pathology. Moreover, α-synuclein fibrils have been recently reported to release soluble and highly toxic oligomeric species, responsible for an immediate dysfunction in the recipient neurons. In this review, we discuss the current knowledge about the plethora of mechanisms of cellular dysfunction caused by α-synuclein oligomers and fibrils, both contributing to neurodegeneration in synucleinopathies.

Key words: amyloid aggregation, neurodegeneration, Parkinson’s disease, protein aggregation, protein misfolding