Targeting α-synuclein: Therapeutic options.
Mov Disord.. 2016-03-01; 31(6): 882-888
DOI: 10.1002/mds.26568
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1. Mov Disord. 2016 Jun;31(6):882-8. doi: 10.1002/mds.26568. Epub 2016 Mar 1.
Targeting α-synuclein: Therapeutic options.
Dehay B(1)(2), Decressac M(3), Bourdenx M(1)(2), Guadagnino I(3), Fernagut
PO(1)(2), Tamburrino A(3), Bassil F(1)(2), Meissner WG(1)(2)(4), Bezard E(1)(2).
Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
(3)Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
(4)Department of Neurology, University Hospital Bordeaux, Bordeaux, France.
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.
© 2016 International Parkinson and Movement Disorder Society.
DOI: 10.1002/mds.26568
PMID: 26926119 [Indexed for MEDLINE]