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| Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives |
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| Author(s): Mattson MP |
| Source: PHYSIOLOGICAL REVIEWS Volume: 77 Issue: 4 Pages: 1081-1132 Published: OCT 1997 |
| Times Cited: 541 References: 594 |
| Abstract: beta-Amyloid precursor protein (beta-APP), the source of the fibrillogenic amyloid beta-peptide (A beta) that accumulates in the brain of victims of Alzheimer's disease, is a multifunctional protein that is widely expressed in the nervous system. beta-Amyloid precursor protein is axonally transported and accumulates in presynaptic terminals and growth cones. A secreted form of beta-APP (sAPP alpha) is released from neurons in response to electrical activity and may function in modulation of neuronal excitability, synaptic plasticity, neurite outgrowth, synaptogenesis, and cell survival. A signaling pathway involving guanosine 3',5'-cyclic monophosphate is activated by sAPP alpha and modulates the activities of potassium channels, methyl-D-aspartate receptors, and the transcription factor NF kappa B. Additional functions of beta-APP may include modulation of cell adhesion and regulation of proliferation of nonneuronal cells. Alternative enzymatic processing of beta-APP liberates A beta, which has a propensity to form amyloid fibrils; A beta can damage and kill neurons and increase their vulnerability to excitotoxicity. The mechanism involves generation of oxyradicals and impairment of membrane transport systems (e.g., ion-motive ATPases and glutamate and glucose transporters). Genetic mutations or age-related metabolic changes may promote neuronal degeneration in Alzheimer's disease by increasing production of A beta and/or decreasing levels of neuroprotective sAPP alpha. |
| Document Type: Review |
| Language: English |
| Reprint Address: Mattson, MP (reprint author), UNIV KENTUCKY, SANDERS BROWN RES CTR AGING, LEXINGTON, KY 40536 USA |
Addresses:
1. UNIV KENTUCKY, DEPT ANAT & NEUROBIOL, LEXINGTON, KY 40536 USA |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Physiology |
| IDS Number: YC320 |
| ISSN: 0031-9333 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |