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
Citations
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Bidirectional relationship between sleep and Alzheimer's disease: role of amyloid, tau, and other factors.
Chanung Wang,David M. Holtzman +1 more
TL;DR: This work postulates a bidirectional relationship between sleep and the neuropathological hallmarks of AD; in particular, the accumulation of amyloid-β (Aβ) and tau and reveals that acute sleep deprivation increases levels of t Tau in mouse brain interstitial fluid and human cerebrospinal fluid and chronic sleep deprivation accelerates the spread of tau protein aggregates in neural networks.
Journal ArticleDOI
Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.
TL;DR: A systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease finds each are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route.
Journal ArticleDOI
Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice.
Jun Tan,Terrence Town,Fiona Crawford,Takashi Mori,Anthony DelleDonne,Robert Crescentini,Demian Obregon,Richard A. Flavell,Michael Mullan +8 more
TL;DR: It is reported that transgenic mice overproducing Aβ, but deficient in CD40L, showed decreased astrocytosis and microgliosis associated with diminished Aβ levels and β-amyloid plaque load, and this findings suggest several possible mechanisms underlying mitigation of AD pathology in response toCD40L depletion.
Journal ArticleDOI
Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases
TL;DR: Recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders such as Alzheimer's disease, Parkinson’s disease, and Huntington's disease are reviewed.
Journal ArticleDOI
Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease
TL;DR: The immune response in the AD brain is regulated by Glial cells, which mediate the peripheral immune response and activation as a therapeutic target in AD is studied.
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
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Journal ArticleDOI
Notch Signaling: Cell Fate Control and Signal Integration in Development
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Journal ArticleDOI
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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