Reference : α-Synuclein in Parkinson's disease: causal or bystander?
Scientific journals : Article
Life sciences : Genetics & genetic processes
Systems Biomedicine
α-Synuclein in Parkinson's disease: causal or bystander?
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Riederer, Peter [University of Wuerzburg, Wuerzburg, Germany > University Hospital, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy]
Berg, Daniela [Christian-Albrechts-Universität, Kiel, Germany > Klinik für Neurologie, UKHS, Campus Kiel,]
Casadei, Nicolas [University of Tübingen, Institute of Medical Genetics and Applied Genomics, Tübingen, Germany > NGS Competence Center Tübingen]
Cheng, Fubo [University of Tübingen, Institute of Medical Genetics and Applied Genomics, Tübingen, Germany > NGS Competence Center Tübingen]
Claßen, Joseph [Universitätsklinikum Leipzig A.ö.R., Leipzig, Germany > Claßen, Klinik und Poliklinik für Neurologie]
Dresel, Christian [Clinical Neurophysiology, Forschungszentrum Translationale Neurowissenschaften (FTN), Rhein-Main-Neuronetz, Germany > Department of Neurology, Center for Movement Disorders, Neuroimaging Center Mainz]
Jost, Wolfgang [Parkinson-Klinik Ortenau, Wolfach, Germany]
Journal of Neural Transmission
Yes (verified by ORBilu)
[en] α-Synuclein ; Parkinson’s disease ; Parkinson’s disease
[en] Parkinson’s disease (PD) comprises a spectrum of disorders with differing subtypes, the vast majority of which share Lewy bodies (LB) as a characteristic pathological hallmark. The process(es) underlying LB generation and its causal trigger molecules are not yet fully understood. α-Synuclein (α-syn) is a major component of LB and SNCA gene missense mutations or duplications/triplications are causal for rare hereditary forms of PD. As typical sporadic PD is associated with LB pathology, a factor of major importance is the study of the α-syn protein and its pathology. α-Syn pathology is, however, also evident in multiple system atrophy (MSA) and Lewy body disease (LBD), making it non-specific for PD. In addition, there is an overlap of these α-synucleinopathies with other protein-misfolding diseases. It has been proven that α-syn, phosphorylated tau protein (pτ), amyloid beta (Aβ) and other proteins show synergistic effects in the underlying pathogenic mechanisms. Multiple cell death mechanisms can induce pathological protein-cascades, but this can also be a reverse process. This holds true for the early phases of the disease process and especially for the progression of PD. In conclusion, while rare SNCA gene mutations are causal for a minority of familial PD patients, in sporadic PD (where common SNCA polymorphisms are the most consistent genetic risk factor across populations worldwide, accounting for 95% of PD patients) α-syn pathology is an important feature. Conversely, with regard to the etiopathogenesis of α-synucleinopathies PD, MSA and LBD, α-syn is rather a bystander contributing to multiple neurodegenerative processes, which overlap in their composition and individual strength. Therapeutic developments aiming to impact on α-syn pathology should take this fact into consideration.
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