Targeting α-synuclein: Therapeutic options
Relevant conflicts of interest/financial disclosures: Dr. Bezard reports personal fees from Motac neuroscience Ltd UK. Dr. Bezard is a shareholder of Motac Holding UK, and Plenitudes SARL France, CROs respectively validating at preclinical stage therapeutic strategies for movement and cognitive disorders and providing management consultancy, that is, with no relationship to the submitted work. Dr. Bezard reports grants from the Michael J. Fox Foundation USA, Fondation de France, Agence Nationale de la recherche France, Framework Program 7 European Commission, Cariplo Foundation, China Science Fund China, Medical Research Council UK, France Parkinson, Institut de Recherche en santé du Canada, outside the submitted work and received honoraria or sponsored/reimbursed travel from Fonds National De la Recherche Luxembourg, Michael J. Fox Foundation, Movement Disorders Society, Parkinson's UK, The New York Academy of Sciences, and World Parkinson's Congress. Dr. Decressac reports grants from the Michael J. Fox Foundation and the Huffington Foundation and received honoraria from the Michael J. Fox Foundation. Prof. Meissner has received teaching honoraria from UCB and TEVA/Lundbeck, travel grants from Abbvie, as well as research support from the Michael J Fox Foundation, the University Hospital Bordeaux, the French Health Ministry, the European Community, ANR, France Parkinson, PSP-France, MSA Coalition, LABEX Excellence Initiative. Dr Fernagut reports grants from France Parkinson and fondation de France. All other authors have nothing to disclose.
Funding agencies: The University of Bordeaux, the Centre National de la Recherche Scientifique, and the Fondazione Telethon provided infrastructural support. This work was supported by Agence Nationale de la Recherche Grants ANR-12-BSV4-0001-01 and LABEX BRAIN ANR-10-LABX-43 (to E.B.), ANR-14-RARE-0001-01 (to W.G.M.), under the framework of E-Rare-2, the ERA-Net for Research on Rare Diseases, and by the Michael J. Fox Foundation (to M.D). M.B. was supported by an MESR fellowship and from the France Parkinson Foundation.
ABSTRACT
The discovery of the central role of α-synuclein (αSyn) in the pathogenesis of Parkinson's disease (PD) has powered, in the last decade, the emergence of novel relevant models of this condition based on viral vector-mediated expression of the disease-causing protein or inoculation of toxic species of αSyn. Although the development of these powerful tools and models has provided considerable insights into the mechanisms underlying neurodegeneration in PD, it has also been translated into the expansion of the landscape of preclinical therapeutic strategies. Much attention is now brought to the proteotoxic mechanisms induced by αSyn and how to block them using strategies inspired by intrinsic cellular pathways such as the enhancement of cellular clearance by the lysosomal-autophagic system, through proteasome-mediated degradation or through immunization. The important effort undertaken by several laboratories and consortia to tackle these issues and identify novel targets warrants great promise for the discovery not only of neuroprotective approaches but also of restorative strategies for PD and other synucleinopathies. In this viewpoint, we summarize the latest advances in this new area of PD research and will discuss promising approaches and ongoing challenges. © 2016 International Parkinson and Movement Disorder Society
