Alpha-synuclein propagation: New insights from animal models.
Aggregation of alpha-synuclein is implicated in several neurodegenerative diseases collectively termed synucleinopathies. Emerging evidence strongly implicates cell-to-cell transmission of misfolded alpha-synuclein as a common pathogenetic mechanism in synucleinopathies. The impact of alpha-synuclein pathology on neuronal dysfunction and behavioral impairments is being explored in animal models. This review provides an update on how research in animal models supports the concept that misfolded alpha-synuclein spreads from cell to cell and describes how findings in animal models might relate to the disease process in humans. Finally, we discuss the current underlying molecular and cellular mechanisms and future therapeutic strategies targeting alpha-synuclein propagation.
Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
Benjamin
B
Dehay
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas, Barcelona, Spain.|Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
Miquel
M
Vila
Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
Erwan
E
Bezard
Laboratory for Translational Parkinson's Disease Research, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, USA.
Patrik
P
Brundin
Department of Neurological Sciences, The Graduate College, Rush University, Chicago, Illinois, USA.
Jeffrey H
JH
Kordower
D000818:Animals; D004195:Disease Models, Animal; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein
Parkinson's disease; alpha-synuclein; animal models; propagation; synucleinopathy