Does dysregulation of the Notch and wingless/Wnt pathways underlie the pathogenesis of Alzheimer's disease?
Alzheimer's disease is characterized by the presence of neurofibrillary tangles and senile neuritic plaques in the brain. Tangles are aggregates of paired helical filaments composed of the microtubule-associated protein, tau, in a hyperphosphorylated state. Senile plaques have a core of amyloid beta-peptide derived by proteolysis of the amyloid precursor protein. A major hurdle in defining the pathogenic mechanisms in Alzheimer's disease is to understand how both amyloid beta-peptide deposition and paired helical filament formation are biochemically linked. Recent genetic discoveries provide some clues, suggesting that components of two developmentally important signalling pathways, Notch and wingless, or the vertebrate homologue of wingless, Wnt, are involved.
Anderton
B H
BH
Department of Neuroscience, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK SE5 8AF. b.anderton@iop.kcl.ac.uk
Dayanandan
R
R
Killick
R
R
Lovestone
S
S
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D053764:Presenilin-1; D053766:Presenilin-2; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase