ISSN:
0265-9247
Keywords:
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Medicine
Notes:
Amyloid β peptide (βA4) accumulates as plaques in the brains of individuals with Alzheimer's disease and Down's syndrome, and may contribute to the cognitive decline that is a feature of these diseases. βA4 is a normal product of cell metabolism, derived from the amyloid precursor protein (APP), but the biological functions of these molecules are not fully known. A hypothetical, descriptive model of the biological interrelationships between βA4 and APP is presented. APPS, the soluble form of APP, which is released at the neuronal surface, and βA4 are envisaged as physiological ligands which have reciprocal paracrine effects on neuronal growth and neurite extension. Differential expression of these factors, manifest as changes in the APPS:βA4 ratio, may therefore have growth-promoting or growth-inhibiting effects on neurons. These effects may be mediated through separate cell-surface interactions but common intracellular effector systems, such as calcium and protein kinase C. In turn, the intracellular events may control the relative production of each ligand from APP through negative feedback loops. Disturbances of these control mechanisms may permit pathological overproduction, and hence accumulation, of βA4. Such a model may also have therapeutic implications.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bies.950170912
Permalink
