Abstract
Alpha-Synuclein (αSyn), a protein highly enriched in neurons where it preferentially localizes at the pre-synapse, has been in the spotlight because its intraneuronal aggregation is a central phenomenon in Parkinson’s disease. However, the consequences of αSyn accumulation to neuronal function are not fully understood. Considering the crucial role of actin on synaptic function and the fact that dysregulation of this cytoskeleton component is emerging in neurodegenerative disorders, the impact of αSyn on actin is a critical point to be addressed. In this review we explore the link between αSyn and actin and its significance for physiology and pathology. We discuss the relevance of αSyn-actin interaction for synaptic function and highlight the actin-depolymerizing protein cofilin-1 as a key player on αSyn-induced actin dysfunction in Parkinson’s disease.
Highlights
In the last years, a large body of evidences point to the neuronal cytoskeleton damage as a major contributor to neurodegeneration (Eira et al, 2016)
Validation of the impact of αSyn on actin dynamics was performed in studies with neuronal cell lines and primary cultures of hippocampal neurons, expressing either WT or A30P αSyn, which demonstrated that physiologically WT αSyn regulates actin dynamics, while the pathologic A30P aSyn disrupts the actin cytoskeleton (Sousa et al, 2009)
Concerning the pathological impact of αSyn on the actin cytoskeleton, further studies showed that the extracellular addition of high concentrations of WT or A30P αSyn to hippocampal neurons induced a stabilization of the actin cytoskeleton, by increasing the number of lamellipodia and filopodia and resistance to depolymerization, with the mutant protein having a more pronounced effect
Summary
A large body of evidences point to the neuronal cytoskeleton damage as a major contributor to neurodegeneration (Eira et al, 2016). Alpha-Synuclein Impacts on Neuronal Actin physiologically and pathologically, an association between the protein and the actin cytoskeleton, a cell component crucial for synaptic function, has been suggested.
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