The opposite variation of GAD67 mRNA in patients with Parkinson's disease, compared with MPTP-treated monkeys, might be explained by the combination of chronic nigrostriatal denervation and long-term L-dopa therapy.
To evaluate the possibility of a shared genetic defect in amyotrophic lateral sclerosis and Parkinson's disease, the SOD1 gene was sequenced in index patients with familial Parkinson's disease from 23 families.No changes were detected.
Molecular genetic studies of the cytochrome P450 system enzyme CYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in large series of patients with Parkinson's disease (PD) when compared with controls.
A defective herpes simplex virus type 1 vector expressing human tyrosine hydroxylase was delivered into the partially denervated striatum of 6-hydroxydopamine-lesioned rats, used as a model of Parkinson's disease.
Analyses of the cytochrome P450 CYP2D6-debrisoquine 4-hydroxylase mutant B allele, a susceptibility gene for PD, revealed a higher representation of this allele in the Lewy body variant of AD than in pure AD or non-AD without Lewy bodies.
We investigated TH polymorphism in 44 patients with sporadic PD, 48 patients with familial PD and 89 of their unaffected relatives, and 50 control subjects.
To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications.
Because dementia in AD and Parkinson's disease (PD) share many biologic and clinical features, we determined the Apo-E genotypes for 79 patients with PD, 22 of whom were demented, and for 44 age-matched healthy elderly controls from the same community.
The data suggest that, in PD: (1) TH protein content is decreased in the surviving nigral dopaminergic neurons, most likely as a result of a lowered TH mRNA cellular content.
Nigra compacta neurons surviving in brains of patients with Parkinson's disease displayed only 57% of the dopamine transporter mRNA hybridization intensity displayed by nigral neurons in normal control brains.
For comparison, a CYP1A1 polymorphism, which is not known to be associated with aberrant drug metabolism, showed no association with Parkinson's disease in our study.
We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM).
ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.