摘要
The misfolding and aggregation of a-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 expe rimental evidence supports the proposition that solu ble oligomeric assemblies,formed during the early phases of the aggregation process,are the major culprits of neuronal toxicity;at the same time,fibrillar confo rmers appear to be the most efficient at propagating among interconnected neurons,thus contributing to the spreading ofα-synuclein pathology.Moreover,α-synuclein fibrils have been recently repo rted 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 byα-synuclein oligome rs and fibrils,both contributing to neurodegeneration in synucleinopathies.
基金
University of Florence(Fondi Ateneo to RC and CC)
Ministry of Education,Universities and Research of Italy(Progetto Dipartimento di Eccellenza to CC)。
