Relationship between multifunctional protein "clusterin" and Alzheimer disease.
In the Alzheimer disease (AD) brain, senile plaques contain several proteins and cytokines, such as beta-amyloid protein (A beta), interleukin 1, transforming growth factor beta 1 (TGF beta 1), and apolipoprotein E, which may contribute to the process of neurodegeneration. Clusterin is also known to colocalize with A beta deposits in neuritic plaques. Clusterin is a multifunctional protein that causes cell aggregation, binds to beta-endorphin, and inhibits the terminal complex formation of complement. Clusterin mRNA and protein are increased in the brains of AD patients. Cytokines such as TGF beta 1 and interleukin 1 enhance the expression of clusterin, which may link clusterin to inflammatory mechanisms in AD. A beta, a 39-43 amino acid peptide, is a major component of the senile plaques that are characteristic of AD. Highly aggregated A beta is implicated in neurodegeneration, e.g., A beta aggregates spontaneously into fibrillar forms resembling those in plaques that, in experimental models, cause neurotoxicity through oxidative stress. Clusterin inhibits the aggregation of A beta, which might be neuroprotective according to the aggregation-toxicity hypothesis of A beta. However, clusterin enhanced the oxidative stress of A beta. This may extend its neurotoxicity to locations distal from plaques wherever A beta is present.
Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
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Choi-Miura
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Oda
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D051152:Clusterin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000378:metabolism*
D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins