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Glucocerebrosidase mutations and the pathogenesis of Parkinson disease.
Ann Med 2013; 45(8):511-21AM

Abstract

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory.

Authors+Show Affiliations

Department of Clinical Neurosciences, University College London Institute of Neurology , London NW3 2PF , United Kingdom.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24219755

Citation

Beavan, Michelle S., and Anthony H V. Schapira. "Glucocerebrosidase Mutations and the Pathogenesis of Parkinson Disease." Annals of Medicine, vol. 45, no. 8, 2013, pp. 511-21.
Beavan MS, Schapira AH. Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. Ann Med. 2013;45(8):511-21.
Beavan, M. S., & Schapira, A. H. (2013). Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. Annals of Medicine, 45(8), pp. 511-21. doi:10.3109/07853890.2013.849003.
Beavan MS, Schapira AH. Glucocerebrosidase Mutations and the Pathogenesis of Parkinson Disease. Ann Med. 2013;45(8):511-21. PubMed PMID: 24219755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucocerebrosidase mutations and the pathogenesis of Parkinson disease. AU - Beavan,Michelle S, AU - Schapira,Anthony H V, PY - 2013/11/14/entrez PY - 2013/11/14/pubmed PY - 2014/7/8/medline SP - 511 EP - 21 JF - Annals of medicine JO - Ann. Med. VL - 45 IS - 8 N2 - Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory. SN - 1365-2060 UR - https://www.unboundmedicine.com/medline/citation/24219755/Glucocerebrosidase_mutations_and_the_pathogenesis_of_Parkinson_disease_ L2 - http://www.tandfonline.com/doi/full/10.3109/07853890.2013.849003 DB - PRIME DP - Unbound Medicine ER -