This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
α-synuclein is a small protein that is mainly expressed in the synaptic terminals of nervous tissue. Although its implication in neurodegeneration is well established, the physiological role of α-synuclein remains elusive. Given its involvement in the modulation of synaptic transmission and the emerging role of microtubules at the synapse, the current study aimed at investigating whether α-synuclein becomes involved with this cytoskeletal component at the presynapse. We first analyzed the expression of α-synuclein and its colocalization with α-tubulin in murine brain. Differences were found between cortical and striatal/midbrain areas, with substantia nigra pars compacta and corpus striatum showing the lowest levels of colocalization. Using a proximity ligation assay, we revealed the direct interaction of α-synuclein with α-tubulin in murine and in human brain. Finally, the previously unexplored interaction of the two proteins in vivo at the synapse was disclosed in murine striatal presynaptic boutons through multiple approaches, from confocal spinning disk to electron microscopy. Collectively, our data strongly suggest that the association with tubulin/microtubules might actually be an important physiological function for α-synuclein in the synapse, thus suggesting its potential role in a neuropathological context.
Alpha-synuclein inclusions are the distinctive trait of brain areas affected by neurodegeneration in Parkinson's disease (PD). Nevertheless, PD is now considered as a multisystemic disorder, since alpha-synuclein pathology has been described also outside the central nervous system. In this regard, the early, non-motor autonomic symptoms point out an important role for the peripheral nervous system during disease progression. On this basis, we propose a review of the alpha-synuclein-related pathological processes observed at peripheral level in PD, starting from molecular mechanisms, through cellular processes to systemic modifications. We discuss their relevance in the etiopathogenesis of the disease, suggesting they are concurrent players in the development of PD, and that the periphery is an easily-accessible window to look at what is occurring in the central nervous system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.