Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides

American Association for the Advancement of Science (AAAS) - Tập 250 Số 4978 - Trang 279-282 - 1990
Bruce A. Yankner1, Lawrence K. Duffy2, Daniel A. Kirschner1
1Departnent of Neurology, Harvard Medical School, Boston, MA 02115 and the Children's Hospital, Boston, MA 02115.
2Department of Chemistry and Institute of Arctic Biology, University of Alaska, Fairbanks, AK 99775-0180.

Tóm tắt

The amyloid β protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid β protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid β protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid β protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid β protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid β protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.

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American Association for the Advancement of Science (AAAS)

Tập 250 Số 4978

279-282

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