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

A review of the possible associations between ambient PM2.5 exposures and the development of Alzheimer's disease

TL;DR: The current work collected and discussed the mechanisms of PM2.5-induced CNS damage and PM2-induced neurodegenerative diseases are discussed.
Journal ArticleDOI

The cell biology of Alzheimer's disease: uncovering the secrets of secretases.

TL;DR: Two essential factors for the proteolytic generation of Abeta have been identified, beta-secretase and the presenilins, which might aid the design of drugs against this disease.
Journal ArticleDOI

Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.

TL;DR: It is shown that the common dietary flavonoid, rutin, can dose-dependently inhibit A β42 fibrillization and attenuate Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells.
Journal ArticleDOI

Immunotherapy for Alzheimer's disease: hoops and hurdles

TL;DR: Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease.
Journal ArticleDOI

Prostaglandins and other lipid mediators in Alzheimer's disease.

TL;DR: This review addresses some current ideas concerning how brain PLA2 and brain PGs are early and key players in acute neural trauma and in brain-cell damage associated with chronic neurodegenerative diseases such as AD.
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)