Regulation of APP Processing Potential for the Therapeutical Reduction of Brain Amyloid Burdena
- 1 January 1996
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 777 (1) , 175-182
- https://doi.org/10.1111/j.1749-6632.1996.tb34416.x
Abstract
The role of brain amyloid in the pathogenesis of Alzheimer's disease (AD) is discussed controversially, but combined genetic and biochemical evidence points to a central role of the gene encoding the amyloid precursor APP in at least some forms of AD. This article proposes that preventing brain amyloid formation is a rational concept for drug treatment of AD. We suggest that pharmacologically active ligands for specific cell surface receptor subtypes—normally stimulated by neurotransmitters, growth factors, and cytokines—constitute a class of chemicals that might be useful to accelerate processing of APP into non‐amyloidogenic, and biologically active, derivatives. This class of agents includes muscarinic m1 and m3 agonists, serotoninergic 5‐HT2a and 5‐HT2c agonists, glutamatergic mGluR1 agonists, as well as agonists for bradykinin and vasopressin receptors.Keywords
This publication has 28 references indexed in Scilit:
- Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's diseaseNature, 1995
- Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie?Cell, 1993
- The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's diseaseBiochemistry, 1993
- Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor proteinNeuron, 1993
- Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein PrecursorScience, 1993
- Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein productionNature, 1992
- Release of Alzheimer Amyloid Precursor Derivatives Stimulated by Activation of Muscarinic Acetylcholine ReceptorsScience, 1992
- The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowthNeuron, 1992
- Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch TypeScience, 1990
- The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesionNeuron, 1989