From Synaptic Physiology to Synaptic Pathology: The Enigma of α-Synuclein

Alpha-synuclein (α-syn) has gained significant attention due to its involvement in neurodegenerative diseases, particularly Parkinson's disease. However, its normal function in the human brain is equally fascinating. The α-syn protein is highly dynamic and can adapt to various conformational stages, which differ in their interaction with synaptic elements, their propensity to drive pathological aggregation, and their toxicity. This review will delve into the multifaceted role of α-syn in different types of synapses, shedding light on contributions to neurotransmission and overall brain function. We describe the physiological role of α-syn at central synapses, including the bidirectional interaction between α-syn and neurotransmitter systems.