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Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder

Parkinson’s disease (PD) by its common understanding is a late-onset sporadic movement disorder. However, there is a need to recognize not only the fact that PD pathogenesis expands beyond (or perhaps to) the brain but also that many early-onset patients develop motor signs before the age of 50 year...

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Autores principales: Kolicheski, Ana, Turcano, Pierpaolo, Tamvaka, Nicole, McLean, Pamela J., Springer, Wolfdieter, Savica, Rodolfo, Ross, Owen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837689/
https://www.ncbi.nlm.nih.gov/pubmed/36502340
http://dx.doi.org/10.3233/JPD-223380
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author Kolicheski, Ana
Turcano, Pierpaolo
Tamvaka, Nicole
McLean, Pamela J.
Springer, Wolfdieter
Savica, Rodolfo
Ross, Owen A.
author_facet Kolicheski, Ana
Turcano, Pierpaolo
Tamvaka, Nicole
McLean, Pamela J.
Springer, Wolfdieter
Savica, Rodolfo
Ross, Owen A.
author_sort Kolicheski, Ana
collection PubMed
description Parkinson’s disease (PD) by its common understanding is a late-onset sporadic movement disorder. However, there is a need to recognize not only the fact that PD pathogenesis expands beyond (or perhaps to) the brain but also that many early-onset patients develop motor signs before the age of 50 years. Indeed, studies have shown that it is likely the protein aggregation observed in the brains of patients with PD precedes the motor symptoms by perhaps a decade. Studies on early-onset forms of PD have shown it to be a heterogeneous disease with multiple genetic and environmental factors determining risk of different forms of disease. Genetic and neuropathological evidence suggests that there are α-synuclein centric forms (e.g., SNCA genomic triplication), and forms that are driven by a breakdown in mitochondrial function and specifically in the process of mitophagy and clearance of damaged mitochondria (e.g., PARKIN and PINK1 recessive loss-of-function mutations). Aligning genetic forms with recognized environmental influences will help better define patients, aid prognosis, and hopefully lead to more accurately targeted clinical trial design. Work is now needed to understand the cross-talk between these two pathomechanisms and determine a sense of independence, it is noted that autopsies studies for both have shown the presence or absence of α-synuclein aggregation. The integration of genetic and environmental data is critical to understand the etiology of early-onset forms of PD and determine how the different pathomechanisms crosstalk.
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spelling pubmed-98376892023-01-30 Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder Kolicheski, Ana Turcano, Pierpaolo Tamvaka, Nicole McLean, Pamela J. Springer, Wolfdieter Savica, Rodolfo Ross, Owen A. J Parkinsons Dis Review Parkinson’s disease (PD) by its common understanding is a late-onset sporadic movement disorder. However, there is a need to recognize not only the fact that PD pathogenesis expands beyond (or perhaps to) the brain but also that many early-onset patients develop motor signs before the age of 50 years. Indeed, studies have shown that it is likely the protein aggregation observed in the brains of patients with PD precedes the motor symptoms by perhaps a decade. Studies on early-onset forms of PD have shown it to be a heterogeneous disease with multiple genetic and environmental factors determining risk of different forms of disease. Genetic and neuropathological evidence suggests that there are α-synuclein centric forms (e.g., SNCA genomic triplication), and forms that are driven by a breakdown in mitochondrial function and specifically in the process of mitophagy and clearance of damaged mitochondria (e.g., PARKIN and PINK1 recessive loss-of-function mutations). Aligning genetic forms with recognized environmental influences will help better define patients, aid prognosis, and hopefully lead to more accurately targeted clinical trial design. Work is now needed to understand the cross-talk between these two pathomechanisms and determine a sense of independence, it is noted that autopsies studies for both have shown the presence or absence of α-synuclein aggregation. The integration of genetic and environmental data is critical to understand the etiology of early-onset forms of PD and determine how the different pathomechanisms crosstalk. IOS Press 2022-12-16 /pmc/articles/PMC9837689/ /pubmed/36502340 http://dx.doi.org/10.3233/JPD-223380 Text en © 2022 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Kolicheski, Ana
Turcano, Pierpaolo
Tamvaka, Nicole
McLean, Pamela J.
Springer, Wolfdieter
Savica, Rodolfo
Ross, Owen A.
Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title_full Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title_fullStr Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title_full_unstemmed Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title_short Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder
title_sort early-onset parkinson’s disease: creating the right environment for a genetic disorder
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837689/
https://www.ncbi.nlm.nih.gov/pubmed/36502340
http://dx.doi.org/10.3233/JPD-223380
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