Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Lancet Neurol. 2015 Aug;14(8):855-866. doi: 10.1016/S1474-4422(15)00006-X. Epub 2015 Jun 3.

Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.

Author information

1
Institute of Neurodegenerative Diseases, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, 33076 Bordeaux, France.
2
Research Unit of Theoretical & Applied Economics, University of Bordeaux, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5113, 33608 Pessac, France.
3
Departments of Neurology, Pathology and Cell Biology, and the Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA.
4
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas, 08035 Barcelona, Spain.
5
Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
6
Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain.
7
ICM, Paris, France; Sorbonne Universités.
8
UPMC Université Paris 06, UM 75, ICM, Paris, France.
9
CNRS, UMR 7225, ICM, Paris, France.
10
Inserm, U 1127, ICM, Paris, France.
11
Molecular Genetics Section and Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD20892, USA.
12
Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10032, USA.
13
TransThera Consulting Co., Zionsville, IN, 46077, USA.
14
Department of Neurology and Feil Family Brain and Mind research Institute, Weill Cornell Medical College, New York NY 10021, USA.
#
Contributed equally

Abstract

Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α-synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson's disease. Most cases occur sporadically, but mutations in several genes, including SNCA, which encodes α-synuclein, are associated with disease development. The discovery and development of therapeutic strategies to block cell death in Parkinson's disease has been limited by a lack of understanding of the mechanisms driving neurodegeneration. However, increasing evidence of multiple pivotal roles of α-synuclein in the pathogenesis of Parkinson's disease has led researchers to consider the therapeutic potential of several strategies aimed at reduction of α-synuclein toxicity. We critically assess the potential of experimental therapies targeting α-synuclein, and discuss steps that need to be taken for target validation and drug development.

PMID:
26050140
PMCID:
PMC5217462
DOI:
10.1016/S1474-4422(15)00006-X
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center