From iPS Cells to Rodents and Nonhuman Primates: Filling Gaps in Modeling Parkinson's Disease.

Autor: Outeiro TF; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany.; Max Planck Institute for Experimental Medicine, Goettingen, Germany.; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK., Heutink P; German Center for Neurodegenerative Diseases, Tübingen, Germany., Bezard E; Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France., Cenci AM; Department of Experimental Medical Science, Basal Ganglia Pathophysiology Unit, Lund University, Lund, Sweden.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2021 Apr; Vol. 36 (4), pp. 832-841. Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1002/mds.28387
Abstrakt: 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 Disorder Society.
(© 2020 International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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