Heat shock proteins and amateur chaperones in amyloid-Beta accumulation and clearance in Alzheimer's disease.
The pathologic lesions of Alzheimer's disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-beta (Abeta) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. "Professional chaperones", such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. "Amateur" chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Abeta, and in the clearance of Abeta from the brain via phagocytosis or active transport across the blood-brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Abeta and tau and in other Abeta-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention.
Wilhelmus
Micha M M
MM
Department of Neurology and Alzheimer Centre, Radboud University Nijmegen Medical Centre, 830 LKN, Nijmegen, 6500 HB, Netherlands.
de Waal
Robert M W
RM
Verbeek
Marcel M
MM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D001053:Apolipoproteins; D006360:Heat-Shock Proteins; D019812:Heparan Sulfate Proteoglycans; D018832:Molecular Chaperones; D003165:Complement System Proteins