Synucleins: New prospects in the diseases of the nervous system

Abstract

Research in the molecular neuroscience field in the last years has revealed a family of proteins called synucleins, present in abundance in the nervous system. Synucleins are small, heat-stable and soluble proteins with a characteristic hydrophobic stretch of 5 to 6 highly conserved, imperfect repeats within the N-terminal. The developmental expression pattern of α and β-synucleins is similar to that of synaptobrevin and synaptophysin, two synaptic proteins with an established and well-characterised role in the physiology of the nervous system and in the development and maturation of synapses in the brain. Regarding the physiological function of synucleins there is substantial evidence that they are involved in the development of the synapses in the brain, in the recycling of the neuro-transmitters (NTs) vesicles, and the regulation of the relative concentrations of the NTs in the synapses, as well as in the mechanisms of cellular communication. However there is no unified and well-characterised model that describes the physiological function of synucleins and their specific role in the physiology of the cell. The various findings come from studies that have examined the proteins under different experimental conditions and thus they are sometimes contradictory. Although the physiological function of synucleins remains elusive, an abundance of studies has examined the relationship of these proteins with a range of neurological and other diseases, especially neurodegenerative diseases and cancer. A group of neurodisorders has been named synucleinopathies, as they are characterised by proteinaceous inclusions in the brains of the patients whose main constituent is α-synuclein. This group includes Alzheimer's disease, Parkinson's disease and multiple sclerosis. This review provides an account of the knowledge about the physiological function of synucleins and describes their implication with pathological conditions, giving specific emphasis on Parkinson's disease.