Raft-partitioning of calcium channels regulates their function

摘要

Alpha-synuclein (Syn) is a cytosolic, soluble, and unstructured protein, which may also associate with membranes by acquiring an α-helical conformation. High Syn concentrations are present in genetic Parkinson disease (PD) due to duplication/triplication of SNCA gene, and are also associated with polymorphisms found in idiopathic PD cases.Syn has been shown to act on several intracellular targets, and to alter synaptic function. The discovery of the presence of Syn in cerebrospinal fluid and of its release from neurons, as demonstrated by numerous studies,suggests that Syn-driven pathology may spread in the brain, although the mechanism of Syn release is still unclear. There is evidence that Syn overexpression modifies the structure of the cellular membrane, however a possible effect of excess Syn on the pre- or post-synaptiC-terminal from the extracellular milieu has yet to be fully analyzed.