Genes implicated in the pathogenesis of Alzheimer's disease.
Both the early and late-onset Alzheimer's disease affect millions of people throughout the world. A number of molecules have been implicated in the pathogenesis of Alzheimer's disease. These include presenilin 1 and 2 (PS1 and PS2), a beta-amyloid peptide, and tau protein. Presenilin 1 and 2 genes implicated in the early-onset familial Alzheimer's disease have been cloned. Both PS1 and PS2 are integral membrane proteins and may function as receptors or channel proteins. Missense mutations in PS1 and PS2 genes have been found in families that cosegregate with early-onset Alzheimer's disease. Overexpression of the mutated PS1 gene produced amyloid plaques in the brain of transgenic mice. Secreted beta-amyloid protein similar to that in the senile plaques of Alzheimer's disease was found to be elevated in fibroblast media from subjects with PS1 or PS2 mutations. Transgenic mice which carried the mutant form of the beta-amyloid precursor protein gene expressed high concentrations of mutant copy of the gene and exhibited abundant amyloid plaques in the brain and memory loss. The mutated PS2 gene enhanced apoptotic activity. This enhanced apoptotic activity may accelerate the process of neurodegeneration leading to an earlier age in the onset of the disease. Identification of lesions in the molecules that are important in the Alzheimer's disease should allow developing therapeutic approaches for its treatment.
Das
H K
HK
Department of Pharmacology, University of North Texas Health Science Center at Fort Worth, Texas 76107, USA. hdas@hsc.unt.edu
Lal
H
H
D017668:Age of Onset; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D017209:Apoptosis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles; D010641:Phenotype; D053764:Presenilin-1; D016875:tau Proteins / Q000235:genetics / Q000502:physiology
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins