α-Synucleinopathy is an umbrella term for a group of neurodegenerative diseases characterized by the appearance of aggregates of the protein α-Synuclein (α-Syn); it includes Parkinson´s disease, multiple-system atrophy, dementia with lewy bodies and pure autonomic failure. All of them lack a causal therapy.
Synucleinopathies are chronic, progressive disorders. Symptoms consist of a decline in motor and cognitive functions and behavioral changes, among others. Notably, symptoms of these diseases significantly overlap with one another, hindering diagnosis.
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α-Syn is a 140-amino acids long naturally unfolded protein widely expressed in central neurons of the brain. α-Syn was originally referred to as PARK1 and PARK4. It is a member of the small protein family of synucleins that are primarily expressed in neural tissue in vertebrates. Interest in the synuclein family intensified after discovering that α-Syn is mutated in some forms of familial Parkinson´s disease. There is increasing evidence demonstrating the propagation of pathological α-Syn to be central to the pathogenesis of synucleinopathies such as Parkinson’s disease and multiple -system atrophy.
The identification of α-Syn as causative agent in synucleinopathies has constituted a significant advance in our understanding of these diseases.
Armed with a strong hypothesis about a common disease inducing event, significant progress in the development of diagnostic measures is expected within the context of the SYMPATH project. In addition, targeting α-Syn has become a rational choice for developing a causative therapy and moreover forms the basis for the TANDEM clinical approach selected by the SYMPATH consortium.