title: Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD?
abstract: Wilson's disease (WD) patients often present with Parkinson's disease (PD). Furthermore, most patients with PD have reduced ceruloplasmin, a characteristic of Wilson's disease. WD is an autosomal recessive disease (requires two faulty copies of a gene to produce a homozygote individual) that afflicts 1 in 1000 people. However, the number of people with one faulty copy (heterozygotes) is much larger, probably about 2% of the population. I hypothesize that the large number of heterozygotes for WD are at greatly increased risk for idiopathic PD, because these people accumulate free copper in the basal ganglia at a slower rate than homozygotes, which accounts for the fact that PD usually develops after 40 years of age. In WD, a ceruloplasmin deficiency results in accumulation of free Cu in the liver, brain, kidneys, etc. The excess Cu results in impaired Zn absorption, which would account for the low levels of Zn in the brains of PD patients. Moreover, the high levels of Fe found in the substantia nigra of PD patients may perhaps be explained by free Cu binding to iron binding protein-1 (IBP-1), causing it to malfunction and preventing it from detaching itself from the transferrin receptor (TfR) inhibition gene, resulting in expression of TfR even when the cell has plenty of Fe. The gradual accumulation of Fe and Cu would explain the damage inflicted on the substantia nigra by free radicals catalyzed by these two metals and which is exacerbated by the low levels of CuZnSOD, due to the Zn deficiency mentioned above. Moreover, if this hypothesis is correct, then PD could be used to help discover the gene (or genes) responsible for WD and vice versa. Furthermore, idiopathic PD could be prevented by identifying the heterozygote individuals and providing them with Zn supplementation, Cu chelation therapy and phlebotomy to eliminate Fe.
authors: sjohnson@qwksilvr.com
authors: S
authors: S
authors: Johnson
mesh_terms: D003300:Copper / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D003300:Copper; D007501:Iron; D014442:Monophenol Monooxygenase