Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation
Author: ["Takashi Saito","Nobuhisa Iwata","Satoshi Tsubuki","Yoshie Takaki","Jiro Takano","Shu-Ming Huang","Takahiro Suemoto","Makoto Higuchi","Takaomi C Saido"]
Publication: Nature Medicine
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Abstract
Expression of somatostatin in the brain declines during aging in various mammals including apes and humans1,2. A prominent decrease in this neuropeptide also represents a pathological characteristic of Alzheimer disease3,4. Using in vitro and in vivo paradigms, we show that somatostatin regulates the metabolism of amyloid β peptide (Aβ), the primary pathogenic agent of Alzheimer disease, in the brain through modulating proteolytic degradation catalyzed by neprilysin. Among various effector candidates, only somatostatin upregulated neprilysin activity in primary cortical neurons. A genetic deficiency of somatostatin altered hippocampal neprilysin activity and localization, and increased the quantity of a hydrophobic 42-mer form of Aβ, Aβ42, in a manner similar to presenilin gene mutations that cause familial Alzheimer disease. These results indicate that the aging-induced downregulation of somatostatin expression may be a trigger for Aβ accumulation leading to late-onset sporadic Alzheimer disease, and suggest that somatostatin receptors may be pharmacological-target candidates for prevention and treatment of Alzheimer disease.
Cite this article
Saito, T., Iwata, N., Tsubuki, S. et al. Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation. Nat Med 11, 434–439 (2005). https://doi.org/10.1038/nm1206
