Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P61278 (
somatostatin
)
22,083
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Expression of
somatostatin
in the brain declines during aging in various mammals including apes and humans. A prominent decrease in this neuropeptide also represents a pathological characteristic of Alzheimer disease. Using in vitro and in vivo paradigms, we show that
somatostatin
regulates the metabolism of amyloid beta peptide (Abeta), 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 Abeta, Abeta(42), 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 Abeta 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.
...
PMID:Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation. 1577 22
