A hypothesis on the aetiology of Alzheimer's disease: description of a model involving a misfolded chaperone.
A model is proposed to explain the aetiology of Alzheimer's disease. It is based on theoretical considerations of protein folding involving molecular chaperones. It explains how a misfolded chaperone gives rise to new misfolded chaperones. Such a protein replicates misfolding and invades the cell. The invasion appears sporadically, its probability increasing with time; a mutation or an increased synthesis of this chaperone shorten the delay before invasion. These characteristics are those of Alzheimer's disease. The model implies that one of the proteins involved in pathogenesis is a molecular chaperone. The possible function as molecular chaperone of the protein expressed by genes involved in the disease is discussed. It is shown that the beta-amyloid precursor protein (APP) as well as apolipoprotein E exhibit some properties of a genuine molecular chaperone. I propose that Alzheimer's disease results from the invasion of the nervous system by a misfolded molecular chaperone.
Liautard
J P
JP
INSERM U-65, Dept Biologie Santé, Université de Montpellier II, France.
D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000502:physiology; D001057:Apolipoproteins E / Q000737:chemistry* / Q000502:physiology; D002883:Chromosomes, Human, Pair 14; D004314:Down Syndrome / Q000150:complications / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D018832:Molecular Chaperones / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D018832:Molecular Chaperones