中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 59-60.doi: 10.4103/1673-5374.264453

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

α-突触核蛋白原纤维形成的研究:现有技术和期望

  

  • 出版日期:2020-01-15 发布日期:2020-05-15

Study of alpha-synuclein fibrillation: state of the art and expectations

Francesca Longhena1, Gaia Faustini1, Arianna Bellucci1,2   

  1. 1Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
    2Laboratory for Preventive and Personalized Medicine, University of Brescia, Brescia, Italy 
  • Online:2020-01-15 Published:2020-05-15
  • Contact: Francesca Longhena, PhD, f.longhena@unibs.it.

摘要: orcid: 0000-0001-6569-9412 (Francesca Longhena)

Abstract: Since the discovery of the presence of fibrillary forms of α-synuclein (α-syn) in Lewy bodies (LB) and Lewy neurites in the brain of patients affected by Parkinson’s disease (PD) and dementia with LB, great effort has been dedicated to study the features of α-syn fibrillation. In parallel, the pathological relevance of the different toxic forms of α-syn has been also matter of investigation. In the last twenty years, scientists have been able to single out that α-syn fibrillation initiates pathological mechanisms that by contributing to or triggering neurodegeneration/neuroinflammation, may lead to PD pathogenesis. This notwithstanding, we still ignore the reasons why α-syn shifts from its natively unfolded conformation to toxic oligomeric and fibrillary forms. The chameleonic nature of monomeric α-syn, and the extremely polymorphic characteristics of aggregated strains, renders it difficult to picture the real nature of α-syn fibrils, their exact composition and formation dynamics. Recently, sophisticated biophysical methods and microscopy techniques have been exploited to study α-syn fibrillation. Here, we provide an overview of the most relevant advancement in our understanding of α-syn fibrils formation and conformation. Nonetheless, numerous techniques and patient- derived experimental models still need to be optimized to actively disclose causes and characteristics of α-syn fibrillation in disease-specific cellular milieux.