title: α-Synuclein elevation in human neurodegenerative diseases: experimental, pathogenetic, and therapeutic implications.
abstract: The discovery of α-synuclein has had profound implications concerning our understanding of Parkinson's disease (PD) and other neurodegenerative disorders characterized by α-synuclein accumulation. In fact, as compared with pre-α-synuclein times, a "new" PD can now be described as a whole-body disease in which a progressive spreading of α-synuclein pathology underlies a wide spectrum of motor as well as nonmotor clinical manifestations. Not only is α-synuclein accumulation a pathological hallmark of human α-synucleinopathies but increased protein levels are sufficient to trigger neurodegenerative processes. α-Synuclein elevations could also be a mechanism by which disease risk factors (e.g., aging) increase neuronal vulnerability to degeneration. An important corollary to the role of enhanced α-synuclein in PD pathogenesis is the possibility of developing α-synuclein-based biomarkers and new therapeutics aimed at suppressing α-synuclein expression. The use of in vitro and in vivo experimental models, including transgenic mice overexpressing α-synuclein and animals with viral vector-mediated α-synuclein transduction, has helped clarify pathogenetic mechanisms and therapeutic strategies involving α-synuclein. These models are not devoid of significant limitations, however. Therefore, further pursuit of new clues on the cause and treatment of PD in this post-α-synuclein era would benefit substantially from the development of improved research paradigms of α-synuclein elevation.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Ayse
authors.initials: A
authors.lastname: Ulusoy
authors.forename: Donato A
authors.initials: DA
authors.lastname: Di Monte
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000008:administration & dosage; D000882:Haplorhini; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D016896:Treatment Outcome; D051844:alpha-Synuclein / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein