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Review Helicobacter hypothesis for idiopathic parkinsonism: before and beyond. 2008
Dobbs RJ, Dobbs SM, Weller C, Charlett A, Bjarnason IT, Curry A, Ellis DS, Ibrahim MA, McCrossan MV, O'Donohue J, Owen RJ, Oxlade NL, Price AB, Sanderson JD, Sudhanva M, Williams J. · Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK. or · Helicobacter. · Pubmed #19250506 No free full text.
Abstract: We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.
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Article Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease. free! 2008
Li Y, Grupe A, Rowland C, Holmans P, Segurado R, Abraham R, Jones L, Catanese J, Ross D, Mayo K, Martinez M, Hollingworth P, Goate A, Cairns NJ, Racette BA, Perlmutter JS, O'Donovan MC, Morris JC, Brayne C, Rubinsztein DC, Lovestone S, Thal LJ, Owen MJ, Williams J. · Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. · Hum Mol Genet. · Pubmed #18063669 links to free full text
Abstract: Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N = 3521, P = 5.38x10(-6), odds ratio (OR) = 1.38 (1.20-1.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N = 1464, P = 0.0145, OR =1.31 (1.05-1.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.
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Article Dynamically responsive intervention for tremor suppression. 2003
Manto M, Topping M, Soede M, Sanchez-Lacuesta J, Harwin W, Pons J, Williams J, Skaarup S, Normie L. · Fonds National de la Recherche Scientifique, Hôpital Erasme-ULB, 808, Route de Lennik, 1070 Bruxelles, Belgium. · IEEE Eng Med Biol Mag. · Pubmed #12845828 No free full text.
This publication has no abstract.
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