alpha-Synuclein and intracellular trafficking: impact on the spreading of Parkinson's disease pathology

Parkinson's disease is characterized by intracellular proteinaceous depositions known as Lewy bodies. These largely consist of the protein alpha-synuclein, whose physiological function remains unclear, but mutations and overexpression of the protein have been shown to cause early onset cases of Parkinson's disease. Deregulation of alpha-synuclein biology causes neurodegeneration and impaired neuronal trafficking, hinting at a possible contribution to the pathological mechanism. Recent studies produced some evidence hinting at the involvement of several regulators of the transport machinery such as Rab GTPases and SNARE proteins, but also shown that alpha-synuclein can be propagated between cells. Here, we discuss the molecular interplay of alpha-synuclein with the intracellular transport machinery, its consequences, and the implications for disease mechanisms.