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Neuroforum

Organ der Neurowissenschaftlichen Gesellschaft

Editor-in-Chief: Wahle, Petra


CiteScore 2018: 0.11

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Volume 25, Issue 2

Issues

Alpha-synuclein as therapeutic target in Parkinson’s disease

Prof. Dr. Franziska Richter Assêncio
  • Corresponding author
  • Chair, Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine Hannover Buenteweg 17, D-30559 Hannover phone: +49-511-953-8720 Fax: +49-511-953-8581 Hannover Germany
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Published Online: 2019-06-04 | DOI: https://doi.org/10.1515/nf-2018-0029

Zusammenfassung

180 Jahre vergingen zwischen James Parkinson’s “An essay on the shaking palsy” und der Entdeckung der zentralen Rolle von alpha-synuclein in der Pathogenese von Parkinson’s disease (PD). Der Identifikation einer PD verursachenden Mutation im alpha-synuclein Gen folgte rasch der Nachweis des Proteins in Lewy Körperchen, den charakteristischen Proteineinschlüssen im Gehirn der Patienten. Trotz vieler ungeklärter Fragen, Forschungsergebnisse zur Entstehung, Ausbreitung und Neurotoxizität der alpha-synuclein Pathologie geben Hoffnung auf die Entwicklung einer Krankheits-modifizierenden Therapie, über die Dopaminersatztherapie hinaus. Die Hypothese, dass alpha-synuclein Pathologie sich ähnlich wie ein Prion ausbreitet, wird kontrovers diskutiert, und initiierte viele interessante neue Forschungsansätze und therapeutische Zielstrukturen. Dieser Übersichtsartikel fasst die Evidenz für eine zentrale Rolle von alpha-synuclein in der Pathogenese der PD zusammen, gefolgt von einer Diskussion neuer Therapiestrategien.

Abstract

It took 180 years from James Parkinson’s descriptions in “An essay on the shaking palsy” to the discovery of alpha-synuclein as key player in Parkinson’s disease (PD). The identification of a PD causing mutation in the gene of alpha-synuclein was followed immediately by detection of its presence in Lewy bodies, inclusions found in the brains of patients. While many open questions remain, findings on how alpha-synuclein pathology emerges, propagates and causes neuronal death provide hope for development of disease-modifying therapeutics beyond the current dopamine replacement therapy. The recent hypothesis of a prion-like transmission of alpha-synuclein pathology raises controversy but also inspired numerous exciting research avenues, partially already translating into novel drug targets. This review summarizes evidence for a critical role of alpha-synuclein in PD pathogenesis followed by a discussion of current promising treatment avenues.

Keywords: synucleinopathy; prion; neurodegeneration; neuroprotection; dopamine

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About the article

Prof. Dr. Franziska Richter Assêncio

Franziska Richter graduated 2007 in Veterinary Medicine (Dr. med. vet.) at the FU Berlin working on animal models of Parkinson´s disease. As a postdoc and research faculty in the lab of Marie-Francoise Chesselet, Department of Neurology at UCLA (2007–2012), she performed several preclinical trials in mouse models of alpha-synuclein pathology. In 2012 she joined Prof. Angelika Richter at the Faculty of Veterinary Medicine in Leipzig, extending her field to therapeutic interventions in dystonia. She is currently Professor and Chair of the Department of Pharmacology, Toxicology and Pharmacy at the University of Veterinary Medicine Hannover.


Published Online: 2019-06-04

Published in Print: 2019-05-27


Citation Information: Neuroforum, Volume 25, Issue 2, Pages 129–136, ISSN (Online) 2363-7013, ISSN (Print) 0947-0875, DOI: https://doi.org/10.1515/nf-2018-0029.

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