Interaction between alpha-synuclein and Rab proteins in health and disease

Intracellular trafficking pathways are extremely complex and need a high degree of regulation to work correctly. In this regard, Rabs are small molecular switches that are involved in many cellular functions, such as regulating vesicle trafficking on all levels, from vesicle formation all the way to vesicle fusion. α-synuclein is a protein, mostly present in nervous tissue, whose function is not fully understood. Nevertheless, it seems to be involved in synaptic activity, mainly neurotransmitters release, reuptake and synaptic vesicle trafficking. In addition, α-synuclein is the main constituent of Lewy bodies, intracellular proteinaceous aggregates that cause neurodegeneration and play a major role in Parkinson’s Disease and related synucleinopathies. We will be analysing the interactions between α-synuclein and Rab proteins in health and disease: in particular how α-synuclein impacts Rab activity, leading to a dysregulation in vesicle trafficking, and how Rabs play a role in α-syn clearance, seeding and spreading.