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Genetic contributions to Parkinson's disease.
Brain Res Brain Res Rev. 2004 Aug; 46(1):44-70.BR

Abstract

Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [alpha-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin-proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease.

Authors+Show Affiliations

Prince of Wales Medical Research Institute and the University of New South Wales, Barker Street, Randwick, Sydney 2031, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15297154

Citation

Huang, Yue, et al. "Genetic Contributions to Parkinson's Disease." Brain Research. Brain Research Reviews, vol. 46, no. 1, 2004, pp. 44-70.
Huang Y, Cheung L, Rowe D, et al. Genetic contributions to Parkinson's disease. Brain Res Brain Res Rev. 2004;46(1):44-70.
Huang, Y., Cheung, L., Rowe, D., & Halliday, G. (2004). Genetic contributions to Parkinson's disease. Brain Research. Brain Research Reviews, 46(1), 44-70.
Huang Y, et al. Genetic Contributions to Parkinson's Disease. Brain Res Brain Res Rev. 2004;46(1):44-70. PubMed PMID: 15297154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic contributions to Parkinson's disease. AU - Huang,Yue, AU - Cheung,Linda, AU - Rowe,Dominic, AU - Halliday,Glenda, PY - 2004/04/05/accepted PY - 2004/8/7/pubmed PY - 2004/10/22/medline PY - 2004/8/7/entrez SP - 44 EP - 70 JF - Brain research. Brain research reviews JO - Brain Res Brain Res Rev VL - 46 IS - 1 N2 - Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [alpha-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin-proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease. UR - https://www.unboundmedicine.com/medline/citation/15297154/Genetic_contributions_to_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165017304000554 DB - PRIME DP - Unbound Medicine ER -