File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease

TitleThe interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease
Authors
KeywordsParkinson’s disease
Genetics
Aging
Environmental toxins
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.translationalneurodegeneration.com/
Citation
Translational Neurodegeneration, 2019, v. 8, p. article no. 23 How to Cite?
AbstractBackground: Parkinson’s disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors. Main body: The prevalence of PD rises exponentially with age, and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death. However, the majority of those over the age of 80 do not have PD, thus other factors in addition to aging are needed to cause disease. Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk. Nevertheless, the causality of most environmental factors is not conclusively established, and alternative explanations such as reverse causality and recall bias cannot be excluded. The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD. Rare mutations as well as common variants in genes such as SNCA, LRRK2 and GBA are associated with risk of PD, but Mendelian causes collectively only account for 5% of PD and common polymorphisms are associated with small increase in PD risk. Heritability of PD has been estimated to be around 30%. Thus, aging, genetics and environmental factors each alone is rarely sufficient to cause PD for most patients. Conclusion: PD is a multifactorial disorder involving interplay of aging, genetics and environmental factors. This has implications on the development of appropriate animal models of PD which take all these factors into account. Common converging pathways likely include mitochondrial dysfunction, impaired autophagy, oxidative stress and neuroinflammation, which are associated with the accumulation and spread of misfolded α-synuclein and neurodegeneration. Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.
Persistent Identifierhttp://hdl.handle.net/10722/279184
ISSN
2017 Impact Factor: 5.872
2015 SCImago Journal Rankings: 1.447
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorPang, SYY-
dc.contributor.authorHo, PWL-
dc.contributor.authorLiu, HF-
dc.contributor.authorLeung, CT-
dc.contributor.authorLi, L-
dc.contributor.authorCHANG, EES-
dc.contributor.authorRamsden, DB-
dc.contributor.authorHo, SL-
dc.date.accessioned2019-10-21T02:21:09Z-
dc.date.available2019-10-21T02:21:09Z-
dc.date.issued2019-
dc.identifier.citationTranslational Neurodegeneration, 2019, v. 8, p. article no. 23-
dc.identifier.issn2047-9158-
dc.identifier.urihttp://hdl.handle.net/10722/279184-
dc.description.abstractBackground: Parkinson’s disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors. Main body: The prevalence of PD rises exponentially with age, and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death. However, the majority of those over the age of 80 do not have PD, thus other factors in addition to aging are needed to cause disease. Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk. Nevertheless, the causality of most environmental factors is not conclusively established, and alternative explanations such as reverse causality and recall bias cannot be excluded. The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD. Rare mutations as well as common variants in genes such as SNCA, LRRK2 and GBA are associated with risk of PD, but Mendelian causes collectively only account for 5% of PD and common polymorphisms are associated with small increase in PD risk. Heritability of PD has been estimated to be around 30%. Thus, aging, genetics and environmental factors each alone is rarely sufficient to cause PD for most patients. Conclusion: PD is a multifactorial disorder involving interplay of aging, genetics and environmental factors. This has implications on the development of appropriate animal models of PD which take all these factors into account. Common converging pathways likely include mitochondrial dysfunction, impaired autophagy, oxidative stress and neuroinflammation, which are associated with the accumulation and spread of misfolded α-synuclein and neurodegeneration. Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.translationalneurodegeneration.com/-
dc.relation.ispartofTranslational Neurodegeneration-
dc.rightsTranslational Neurodegeneration. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectParkinson’s disease-
dc.subjectGenetics-
dc.subjectAging-
dc.subjectEnvironmental toxins-
dc.titleThe interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease-
dc.typeArticle-
dc.identifier.emailPang, SYY: syypang@hku.hk-
dc.identifier.emailHo, PWL: hwl2002@hku.hk-
dc.identifier.emailLiu, HF: liuhf@hku.hk-
dc.identifier.emailLeung, CT: gctleung@hku.hk-
dc.identifier.emailHo, SL: slho@hku.hk-
dc.identifier.authorityHo, PWL=rp00259-
dc.identifier.authorityHo, SL=rp00240-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s40035-019-0165-9-
dc.identifier.pmid31428316-
dc.identifier.pmcidPMC6696688-
dc.identifier.scopuseid_2-s2.0-85071047232-
dc.identifier.hkuros307331-
dc.identifier.volume8-
dc.identifier.spagearticle no. 23-
dc.identifier.epagearticle no. 23-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats