Universität zu Köln

Riederer, Peter, Berg, Daniela, Casadei, Nicolas, Cheng, Fubo, Classen, Joseph ORCID: 0000-0001-7182-6967, Dresel, Christian ORCID: 0000-0002-0632-7085, Jost, Wolfgang, Krueger, Rejko, Mueller, Thomas, Reichmann, Heinz, Riess, Olaf, Storch, Alexander, Strobel, Sabrina, van Eimeren, Thilo, Voelker, Hans-Ullrich, Winkler, Juergen, Winklhofer, Konstanze F., Wuellner, Ullrich, Zunke, Friederike ORCID: 0000-0002-0408-6388 and Monoranu, Camelia-Maria (2019). alpha-Synuclein in Parkinson's disease: causal or bystander? J. Neural Transm., 126 (7). S. 815 - 841. WIEN: SPRINGER WIEN. ISSN 1435-1463

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Abstract

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. alpha-Synuclein (alpha-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 alpha-syn protein and its pathology. alpha-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 alpha-synucleinopathies with other protein-misfolding diseases. It has been proven that alpha-syn, phosphorylated tau protein (p tau), amyloid beta (A beta) 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) alpha-syn pathology is an important feature. Conversely, with regard to the etiopathogenesis of alpha-synucleinopathies PD, MSA and LBD, alpha-syn is rather a bystander contributing to multiple neurodegenerative processes, which overlap in their composition and individual strength. Therapeutic developments aiming to impact on alpha-syn pathology should take this fact into consideration.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Riederer, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Berg, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Casadei, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheng, Fubo UNSPECIFIED UNSPECIFIED UNSPECIFIED Classen, Joseph UNSPECIFIED orcid.org/0000-0001-7182-6967 UNSPECIFIED Dresel, Christian UNSPECIFIED orcid.org/0000-0002-0632-7085 UNSPECIFIED Jost, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Rejko UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Reichmann, Heinz UNSPECIFIED UNSPECIFIED UNSPECIFIED Riess, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Storch, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Strobel, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED van Eimeren, Thilo UNSPECIFIED UNSPECIFIED UNSPECIFIED Voelker, Hans-Ullrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Winklhofer, Konstanze F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuellner, Ullrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Zunke, Friederike UNSPECIFIED orcid.org/0000-0002-0408-6388 UNSPECIFIED Monoranu, Camelia-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136227
DOI:	10.1007/s00702-019-02025-9
Journal or Publication Title:	J. Neural Transm.
Volume:	126
Number:	7
Page Range:	S. 815 - 841
Date:	2019
Publisher:	SPRINGER WIEN
Place of Publication:	WIEN
ISSN:	1435-1463
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUBSTANTIA-NIGRA NEUROMELANIN; POSTTRANSLATIONAL PROTEIN HYDROXYLATION; NIGROSTRIATAL DOPAMINE DEPLETION; GENOME-WIDE ASSOCIATION; MEMBRANE-BINDING; NEURONAL VULNERABILITY; BIOINORGANIC CHEMISTRY; OXIDATIVE STRESS; GUT MICROBIOTA; LEWY BODIES Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13622