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Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease
Parkinson’s disease (PD) is primarily idiopathic and a highly heterogenous neurodegenerative disease with patients experiencing a wide array of motor and non-motor symptoms. A major challenge for understanding susceptibility to PD is to determine the genetic and environmental factors that influence...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689743/ https://www.ncbi.nlm.nih.gov/pubmed/36360174 http://dx.doi.org/10.3390/genes13111937 |
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author | Kim, Jeffrey Daadi, Etienne W. Oh, Thomas Daadi, Elyas S. Daadi, Marcel M. |
author_facet | Kim, Jeffrey Daadi, Etienne W. Oh, Thomas Daadi, Elyas S. Daadi, Marcel M. |
author_sort | Kim, Jeffrey |
collection | PubMed |
description | Parkinson’s disease (PD) is primarily idiopathic and a highly heterogenous neurodegenerative disease with patients experiencing a wide array of motor and non-motor symptoms. A major challenge for understanding susceptibility to PD is to determine the genetic and environmental factors that influence the mechanisms underlying the variations in disease-associated traits. The pathological hallmark of PD is the degeneration of dopaminergic neurons in the substantia nigra pars compacta region of the brain and post-mortem Lewy pathology, which leads to the loss of projecting axons innervating the striatum and to impaired motor and cognitive functions. While the cause of PD is still largely unknown, genome-wide association studies provide evidence that numerous polymorphic variants in various genes contribute to sporadic PD, and 10 to 15% of all cases are linked to some form of hereditary mutations, either autosomal dominant or recessive. Among the most common mutations observed in PD patients are in the genes LRRK2, SNCA, GBA1, PINK1, PRKN, and PARK7/DJ-1. In this review, we cover these PD-related mutations, the use of induced pluripotent stem cells as a disease in a dish model, and genetic animal models to better understand the diversity in the pathogenesis and long-term outcomes seen in PD patients. |
format | Online Article Text |
id | pubmed-9689743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96897432022-11-25 Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease Kim, Jeffrey Daadi, Etienne W. Oh, Thomas Daadi, Elyas S. Daadi, Marcel M. Genes (Basel) Review Parkinson’s disease (PD) is primarily idiopathic and a highly heterogenous neurodegenerative disease with patients experiencing a wide array of motor and non-motor symptoms. A major challenge for understanding susceptibility to PD is to determine the genetic and environmental factors that influence the mechanisms underlying the variations in disease-associated traits. The pathological hallmark of PD is the degeneration of dopaminergic neurons in the substantia nigra pars compacta region of the brain and post-mortem Lewy pathology, which leads to the loss of projecting axons innervating the striatum and to impaired motor and cognitive functions. While the cause of PD is still largely unknown, genome-wide association studies provide evidence that numerous polymorphic variants in various genes contribute to sporadic PD, and 10 to 15% of all cases are linked to some form of hereditary mutations, either autosomal dominant or recessive. Among the most common mutations observed in PD patients are in the genes LRRK2, SNCA, GBA1, PINK1, PRKN, and PARK7/DJ-1. In this review, we cover these PD-related mutations, the use of induced pluripotent stem cells as a disease in a dish model, and genetic animal models to better understand the diversity in the pathogenesis and long-term outcomes seen in PD patients. MDPI 2022-10-25 /pmc/articles/PMC9689743/ /pubmed/36360174 http://dx.doi.org/10.3390/genes13111937 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kim, Jeffrey Daadi, Etienne W. Oh, Thomas Daadi, Elyas S. Daadi, Marcel M. Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title | Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title_full | Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title_fullStr | Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title_full_unstemmed | Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title_short | Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson’s Disease |
title_sort | human induced pluripotent stem cell phenotyping and preclinical modeling of familial parkinson’s disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689743/ https://www.ncbi.nlm.nih.gov/pubmed/36360174 http://dx.doi.org/10.3390/genes13111937 |
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