Gaucher disease and parkinsonism, a molecular link theory.
Mutant GBA was found recently to be the most prevalent risk factor for familial parkinsonism. The two diseases do not share common symptoms and there is no direct pathway to explain the mechanism by which GBA mutations can confer the risk. Increased burden on the degradative pathway caused by defective glucocerebrosidase, or toxic side effects of glycosylated lipids accumulation were proposed to explain brain damage. Both hypotheses are not sufficient to explain the linkage. In order to develop a more inclusive theory we introduced into the model the prion theory and the second hit. Other possibilities are also brought into consideration.
Goldin
Ehud
E
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA. goldine@mail.nih.gov
D000818:Animals; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics*
D005962:Glucosylceramidase
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