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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Journal ArticleDOI
Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies
Jessica Nasica-Labouze,Phuong H. Nguyen,Fabio Sterpone,Olivia Berthoumieu,Nicolae-Viorel Buchete,Sébastien Côté,Alfonso De Simone,Andrew J. Doig,Peter Faller,Angel E. Garcia,Alessandro Laio,Mai Suan Li,Simone Melchionna,Normand Mousseau,Yuguang Mu,Anant K. Paravastu,Samuela Pasquali,David J. Rosenman,Birgit Strodel,Bogdan Tarus,John H. Viles,Tong Zhang,Tong Zhang,Chunyu Wang,Philippe Derreumaux,Philippe Derreumaux +25 more
TL;DR: Simulations Complement Experimental Studies Jessica Nasica-Labouze, Phuong H. Nguyen, Fabio Sterpone,† Olivia Berthoumieu,‡ Nicolae-Viorel Buchete, Sebastien Cote, Alfonso De Simone, Andrew J. Doig, and Philippe Derreumaux are authors of this paper.
Journal ArticleDOI
Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease
Marcus J. Calkins,Maria Manczak,Peizhong Mao,Ulziibat Shirendeb,P. Hemachandra Reddy,P. Hemachandra Reddy +5 more
TL;DR: The results revealed an accumulation of intraneuronal oligomeric Aβ, leading to mitochondrial and synaptic deficiencies, and ultimately causing neurodegeneration in AβPP cultures, but found that the mitochondria-targeted antioxidant SS31 restored mitochondrial transport and synaptic viability, and decreased the percentage of defective mitochondria, indicating that SS31 protects mitochondria and synapses from Aβ toxicity.
Journal ArticleDOI
Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment
TL;DR: The role of Abeta in the pathogenesis of AD is discussed and also the use of redox proteomics to identify oxidatively modified brain proteins in AD and mild cognitive impairment is discussed.
Book ChapterDOI
Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. The role of amyloid in dementia and stroke
Blas Frangione,Jorge Ghiso +1 more
TL;DR: Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidsosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the ameloid protein.
Journal ArticleDOI
Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.
Lilian Calderón-Garcidueñas,William Reed,Robert R. Maronpot,Carlos Henríquez-Roldán,Ricardo Delgado-Chávez,Ana Laura Calderón-Garcidueñas,Irma Dragustinovis,Maricela Franco-Lira,Mariana Aragón-Flores,Anna C. Solt,Michael K. Altenburg,Ricardo Torres-Jardón,James A. Swenberg +12 more
TL;DR: Exposure to severe airpollution is associated with brain inflammation and Aβ 42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.
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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Journal ArticleDOI
Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
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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
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Journal ArticleDOI
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
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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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