From iPS Cells to Rodents and Nonhuman Primates: Filling Gaps in Modeling Parkinson’s Disease.
Mov Disord. 2020-11-16; :
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Outeiro TF(1)(2)(3), Heutink P(4), Bezard E(5)(6), Cenci AM(7).
(1)Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany.
(2)Max Planck Institute for Experimental Medicine, Goettingen, Germany.
(3)Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
(4)German Center for Neurodegenerative Diseases, Tübingen, Germany.
(5)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
(6)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
(7)Department of Experimental Medical Science, Basal Ganglia Pathophysiology Unit, Lund University, Lund, Sweden.
Parkinson’s disease (PD) is primarily known as a movement disorder because of
typical clinical manifestations associated with the loss of dopaminergic neurons
in the substantia nigra. However, it is now widely recognized that PD is a much
more complex condition, with multiple and severe nonmotor features implicating
additional brain areas and organs in the disease process. Pathologically, typical
forms of PD are characterized by the accumulation of α-synuclein-rich protein
inclusions known as Lewy bodies and Lewy neurites, although other types of
protein inclusions are also often present in the brain. Familial forms of PD have
provided a wealth of information about molecular pathways leading to
neurodegeneration, but only to add to the complexity of the problem and uncover
new knowledge gaps. Therefore, modeling PD in the laboratory has become
increasingly challenging. Here, we discuss knowledge gaps and challenges in the
use of laboratory models for the study of a disease that is clinically
heterogeneous and multifactorial. We propose that the combined use of
patient-derived cells and animal models, along with current technological tools,
will not only expand our molecular and pathophysiological understanding of PD,
but also assist in the identification of therapeutic strategies targeting
relevant pathogenic pathways. © 2020 International Parkinson and Movement
© 2020 International Parkinson and Movement Disorder Society.