Subcellular localization of alpha-synuclein aggregates and their interaction with membranes
For more than a decade numerous evidence has been reported on the mechanisms of toxicity of α-synuclein (αS) oligomers and aggregates in α-synucleinopathies.These species were thought to form freely in the cytoplasm but recent reports of αS multimer conformations when bound to synaptic vesicles in physiological conditions, have raised the question about where αS aggregation initiates.In this review we focus on recent literature regarding the impact on membrane binding and subcellular localization of αS toxic species to understand how regular cellular function of αS contributes to pathology.Notably αS has been reported to mainly associate with specific membranes in neurons such as those of synaptic vesicles, ER/Golgi and the mitochondria, while toxic species of αS have been shown to inhibit, among others, neurotransmission,protein trafficking and mitochondrial function.Strategies interfering with αS membrane binding have shown to improve αS-driven toxicity in worms and in mice.Thus, a selective membrane binding that would result in a specific subcellular localization could be the key to understand how aggregation and pathology evolves, pointing out to αS functions that are primarily affected before onset of irreversible damage.
alpha-synuclein oligomers aggregates subcellular localization membranes binding Parkinsons disease neurodegeneration alpha-synucleinopathies
Fabiana Miraglia Alessio Ricci Lucia Rota Emanuela Colla
Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy;Department of Pharmacy, University of Pisa Bio@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy
国际会议
广州
英文
159-167
2018-07-26（万方平台首次上网日期，不代表论文的发表时间）