Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TLDR
Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.Abstract:
Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...read more
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Journal ArticleDOI
Nitric oxide and nitroxidative stress in Alzheimer's disease.
TL;DR: The functions of NO and the potential role of NO/O2-/ONOO- induced nitroxidative stress in neuronal and endothelial degeneration observed in Alzheimer's disease are reviewed.
Journal ArticleDOI
Neuronal Ca2+/calmodulin-dependent protein kinase II--discovery, progress in a quarter of a century, and perspective: implication for learning and memory.
TL;DR: The molecular structure, properties and functions of CaM kinase II, as a major component of neurons, are presented, based mainly developed on findings made in the laboratory.
Cellular prion protein regulates -secretase cleavage of the Alzheimer's amyloid precursor protein
Edward T. Parkin,Nicole T. Watt,Ishrut Hussain,Elizabeth A. Eckman,Christopher B. Eckman,Jean Manson,Herbert Baybutt,Anthony J. Turner,Nigel M. Hooper +8 more
TL;DR: In this article, the proteinolysis research group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, United Kingdom.
Journal ArticleDOI
Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging.
TL;DR: Heme deficiency or dysregulation may be an important and preventable component of the neurodegenerative process and could result from its interaction with heme regulatory motifs in specific proteins or secondary to the compromised mitochondria.
Journal ArticleDOI
Interaction of Reelin with Amyloid Precursor Protein Promotes Neurite Outgrowth
Hyang-Sook Hoe,Kea Joo Lee,Rosalind S. E. Carney,Jiyeon Lee,Alexandra Markova,Ji-Yun Lee,Brian W. Howell,Bradley T. Hyman,Daniel T.S. Pak,Guojun Bu,G. William Rebeck +10 more
TL;DR: It is demonstrated that Reelin interacts with APP, potentially having important effects on neurite development, as APP and Reelin have previously been shown to promote neurite outgrowth through interactions with integrins.
References
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Journal ArticleDOI
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
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Notch Signaling: Cell Fate Control and Signal Integration in Development
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Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
George G. Glenner,Caine W. Wong +1 more
TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
Journal ArticleDOI
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Jie Kang,H. G. Lemaire,A. Unterbeck,J. M. Salbaum,Colin L. Masters,K.-H. Grzeschik,Gerd Multhaup,Konrad Beyreuther,Benno Müller-Hill +8 more
TL;DR: An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
Journal ArticleDOI
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
Alison Goate,Marie-Christine Chartier-Harlin,Michael Mullan,Jeremy P Brown,Fiona Crawford,Liana Fidani,L. Giuffra,Andrew Haynes,N.G. Irving,Louise James,R. Mant,Phillippa Newton,Karen Rooke,P Roques,Christopher Talbot,Margaret A. Pericak-Vance,Alien D. Roses,Robert Williamson,Martin N. Rossor,Michael John Owen,John Hardy +20 more
TL;DR: A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene as discussed by the authors, which suggests that some cases of AD could be caused by mutations in the APP gene.
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