scispace - formally typeset
Journal ArticleDOI

Alzheimer's Disease: Genes, Proteins, and Therapy

Dennis J. Selkoe
- 01 Apr 2001 - 
- Vol. 81, Iss: 2, pp 741-766
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
More filters
Journal ArticleDOI

Anti-amyloidogenic effects of antioxidants: implications for the prevention and therapeutics of Alzheimer's disease.

TL;DR: The recent advances in the research on the antioxidants that inhibit the formation of fAbeta, as well as destabilize preformed f Abeta are reviewed to suggest they could be key molecules for the development of preventives and therapeutics for AD.
Journal ArticleDOI

Lipid Rafts and Alzheimer’s Disease: Protein-Lipid Interactions and Perturbation of Signaling

TL;DR: Modulation of APP cleavage by lipid rafts and their components is discussed, while also looking at more recent findings on the role of lipid rafting in signaling events.
Journal ArticleDOI

The various aggregation states of beta-amyloid 1-42 mediate different effects on oxidative stress, neurodegeneration, and BACE-1 expression.

TL;DR: It is found that prefibrillar and oligomeric A beta(1-42) resulted in a more dramatic increase in the oxidative stress markers 4-hydroxynonenal and hydrogen peroxide compared to fibrillsar A beta (1- 42), which resulted in the more rapid and significant induction of both apoptotic and necrotic neuronal cell death.
Journal ArticleDOI

Ageing of the brain.

TL;DR: The brains of individuals who are cognitively normal show age-related changes that include an overall reduction in the brain volume and weight and enlargement of the brain ventricles, but the interplay between genetic and environmental factors probably determines the degree of pathological brain ageing and whether or not individuals develop dementia.
Journal ArticleDOI

A High-Throughput Screen for Compounds That Inhibit Aggregation of the Alzheimer's Peptide

TL;DR: A novel high-throughput screen capable of isolating inhibitors of Abeta aggregation from large libraries of inactive candidates and confirmed that the selected compound inhibits aggregation of synthetic Abeta42 peptide.
References
More filters
Journal ArticleDOI

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families

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

TL;DR: Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development, providing a general developmental tool to influence organ formation and morphogenesis.
Journal ArticleDOI

Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein

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

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.

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.
Related Papers (5)