Direct Binding And Functional Coupling Of α-synuclein To Vesicular Monoamine Transporter-2

Parkinson's disease (PD) is a neurodegenerative disorder that results from the loss of dopamine (DA)-containing neurons projecting from the substantia nigra to the dorsal striatum. a-synuclein is a major component in Lewy bodies, a neuropathological hallmark of PD. Although PD etiology remains unknown, evidence points to a role for a-synuclein, a presynaptic protein of undetermined function. Familial PD can result from a-synuclein gene mutations, producing A53T or A30P amino acid changes. Although overexpression of human a-synuclein induces dopaminergic nerve terminal degeneration, the molecular mechanism by which a-synuclein contributes to the degeneration of these pathways remains enigmatic.A leading hypothesis is the generation of reactive oxygen species (ROS) released from the oxidative metabolism of DA, that may, in turn, cause damage to cellular protein, lipid, and DNA elements and dopamine (DA) metabolism or oxidative phosphorylation produce reactive oxygen species (ROS) and inhibit complex I of the mitochondrial respiratory chain, which is likely responsible for the neuron degeneration. Evidences show that a-synuclein selectively damages the dopaminergic neuron and plays important role on the DA metabolization...