{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:56:55Z","timestamp":1791403015525,"version":"4.3.3"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2005,3,20]],"date-time":"2005-03-20T00:00:00Z","timestamp":1111276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2005,4]]},"DOI":"10.1038\/nm1206","type":"journal-article","created":{"date-parts":[[2005,3,20]],"date-time":"2005-03-20T18:11:43Z","timestamp":1111342303000},"page":"434-439","source":"Crossref","is-referenced-by-count":321,"title":["Somatostatin regulates brain amyloid \u03b2 peptide A\u03b242 through modulation of proteolytic degradation"],"prefix":"10.1038","volume":"11","author":[{"given":"Takashi","family":"Saito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tsubuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Takaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Takano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Suemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C","family":"Saido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,3,20]]},"reference":[{"key":"BFnm1206_CR1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0006-8993(96)01317-0","volume":"749","author":"M Hayashi","year":"1997","unstructured":"Hayashi, M., Yamashita, A. & Shimizu, K. Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate brain: decreased levels of mRNA during aging. Brain Res. 749, 283\u2013289 (1997).","journal-title":"Brain Res."},{"key":"BFnm1206_CR2","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nature02661","volume":"429","author":"T Lu","year":"2004","unstructured":"Lu, T. et al. Gene regulation and DNA damage in the ageing human brain. Nature 429, 883\u2013891 (2004).","journal-title":"Nature"},{"key":"BFnm1206_CR3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/288279a0","volume":"288","author":"P Davies","year":"1980","unstructured":"Davies, P., Katzman, R. & Terry, R.D. Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer senile dementia. Nature 288, 279\u2013280 (1980).","journal-title":"Nature"},{"key":"BFnm1206_CR4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-002-0551-7","volume":"104","author":"JAP van de Nes","year":"2002","unstructured":"van de Nes, J.A.P., Sandmann-Keil, D. & Braak, H. Interstitial cells subjacent to the entorhinal region expressing somatostatin-28 immunoreactivity are susceptible to development of Alzheimer's disease\u2013related cytoskeletal changes. Acta Neuropathol. 104, 351\u2013356 (2002).","journal-title":"Acta Neuropathol."},{"key":"BFnm1206_CR5","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy, J. & Selkoe, D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353\u2013356 (2002).","journal-title":"Science"},{"key":"BFnm1206_CR6","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/72237","volume":"6","author":"N Iwata","year":"2000","unstructured":"Iwata, N. et al. (2000). Identification of the major A\u03b21 \u2013 42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nat. Med. 6, 143\u2013151 (2000).","journal-title":"Nat. Med."},{"key":"BFnm1206_CR7","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1126\/science.1059946","volume":"292","author":"N Iwata","year":"2001","unstructured":"Iwata, N. et al. Metabolic regulation of brain A\u03b2 by neprilysin. Science 292, 1550\u20131552 (2001).","journal-title":"Science"},{"key":"BFnm1206_CR8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/jnr.10390","volume":"70","author":"N Iwata","year":"2002","unstructured":"Iwata, N., Takaki, Y., Fukami, S., Tsubuki, S. & Saido, T.C. Region-specific reduction of A\u03b2-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging. J. Neurosci. Res. 70, 493\u2013500 (2002).","journal-title":"J. Neurosci. Res."},{"key":"BFnm1206_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0304-3940(00)01675-X","volume":"297","author":"K Yasojima","year":"2001","unstructured":"Yasojima, K., Akiyama, H., McGeer, E.G. & McGeer, P.L. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of \u03b2-amyloid peptide. Neurosci. Lett. 297, 97\u2013100 (2001).","journal-title":"Neurosci. Lett."},{"key":"BFnm1206_CR10","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/S0896-6273(03)00787-6","volume":"40","author":"MA Leissring","year":"2003","unstructured":"Leissring, M.A. et al. Enhanced proteolysis of \u03b2-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40, 1087\u20131093 (2003).","journal-title":"Neuron"},{"key":"BFnm1206_CR11","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1523\/JNEUROSCI.4792-03.2004","volume":"24","author":"N Iwata","year":"2004","unstructured":"Iwata, N. et al. Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-\u03b2 peptide in mouse brain. J. Neurosci. 24, 991\u2013998 (2004).","journal-title":"J. Neurosci."},{"key":"BFnm1206_CR12","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S0008-6363(98)00192-8","volume":"40","author":"T-L Wang","year":"1998","unstructured":"Wang, T.-L., Chang, H., Hung, C.-R. & Tseng, Y.-Z. Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction. Cardiovasc. Res. 40, 557\u2013563 (1998).","journal-title":"Cardiovasc. Res."},{"key":"BFnm1206_CR13","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1182\/blood.V98.9.2697","volume":"98","author":"DD Joshi","year":"2001","unstructured":"Joshi, D.D. et al. Negative feedback on the effect of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study. Blood 98, 2697\u20132706 (2001).","journal-title":"Blood"},{"key":"BFnm1206_CR14","doi-asserted-by":"publisher","first-page":"30259","DOI":"10.1074\/jbc.M401891200","volume":"279","author":"E Hama","year":"2004","unstructured":"Hama, E., Shirotani, K., Iwata, N. & Saido, T.C. Effects of neprilysin chimeric proteins targeted to subcellular compartments on amyloid \u03b2 peptide clearance in primary neurons. J. Biol. Chem. 279, 30259\u201330269 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFnm1206_CR15","doi-asserted-by":"publisher","first-page":"21895","DOI":"10.1074\/jbc.M008511200","volume":"276","author":"K Shirotani","year":"2001","unstructured":"Shirotani, K. et al. Neprilysin degrades both amyloid \u03b2 peptides 1\u201340 and 1\u201342 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. J. Biol. Chem. 276, 21895\u201321901 (2001).","journal-title":"J. Biol. Chem."},{"key":"BFnm1206_CR16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0006-8993(01)02563-X","volume":"906","author":"T Zeyda","year":"2001","unstructured":"Zeyda, T., Diehl, N., Paylor, R., Brennan, M.B. & Hochgeschwender, U. Impairment in motor learning of somatostatin null mutant mice. Brain Res. 906, 107\u2013114 (2001).","journal-title":"Brain Res."},{"key":"BFnm1206_CR17","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1172\/JCI119225","volume":"99","author":"I Shimon","year":"1997","unstructured":"Shimon, I. et al. Somatostatin receptor subtype specificity in human fetal pituitary cultures. J. Clin. Invest. 99, 789\u2013798 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFnm1206_CR18","first-page":"7","volume":"2","author":"A Garcia-Jimenez","year":"2002","unstructured":"Garcia-Jimenez, A., Fastbom, J., Winbland, B. & Cowburn, R.F. G-protein regulation of signal transduction in Alzheimer's disease. Brain Aging 2, 7\u201315 (2002).","journal-title":"Brain Aging"},{"key":"BFnm1206_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0005-2736(03)00235-9","volume":"1616","author":"LN Moller","year":"2003","unstructured":"Moller, L.N., Stidsen, C.E., Hartmann, B. & Holst, J.J. Somatostatin receptors. Biochim. Biophys. Acta 1616, 1\u201384 (2003).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnm1206_CR20","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/28190","volume":"394","author":"G Miesenbock","year":"1998","unstructured":"Miesenbock, G., De Angelis, D.A. & Rothman, J.E. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394, 192\u2013195 (1998).","journal-title":"Nature"},{"key":"BFnm1206_CR21","doi-asserted-by":"publisher","first-page":"11151","DOI":"10.1073\/pnas.89.23.11151","volume":"89","author":"JF Bruno","year":"1992","unstructured":"Bruno, J.F., Xu, Y., Song, J. & Berelowitz, M. Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc. Natl. Acad. Sci. USA 89, 11151\u201311155 (1992).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm1206_CR22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1517\/13543784.13.1.69","volume":"13","author":"SA Doggrell","year":"2004","unstructured":"Doggrell, S.A. The potential of activation of somatostatinergic neurotransmission with FK960 in Alzheimer's disease. Expert Opin. Investig. Drugs 13, 69\u201372 (2004).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"BFnm1206_CR23","first-page":"17","volume-title":"A\u03b2 Metabolism and Alzheimer's Disease","author":"M Citron","year":"2003","unstructured":"Citron, M. \u03b2-Secretase: progress and open questions. in A\u03b2 Metabolism and Alzheimer's Disease. (ed. Saido, T.C.) 17\u201325 (Landes Bioscience, Georgetown, 2003)."},{"key":"BFnm1206_CR24","first-page":"33","volume-title":"A\u03b2 Metabolism and Alzheimer's Disease","author":"MS Wolfe","year":"2003","unstructured":"Wolfe, M.S. \u03b3-Secretase and presenilin. in A\u03b2 Metabolism and Alzheimer's Disease. (ed. Saido, T.C.) 33\u201347 (Landes Bioscience, Georgetown, 2003)."},{"key":"BFnm1206_CR25","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1093\/oxfordjournals.jbchem.a003040","volume":"130","author":"E Hama","year":"2001","unstructured":"Hama, E. et al. Clearance of extracellular and cell-associated amyloid \u03b2 peptide by viral expression of neprilysin in primary culture. J. Biochem. 130, 721\u2013726 (2001).","journal-title":"J. Biochem."},{"key":"BFnm1206_CR26","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1523\/JNEUROSCI.09-12-04439.1989","volume":"9","author":"SA Back","year":"1989","unstructured":"Back, S.A. & Gorestein, C. Histochemical visualization of neutral endopeptidase-24.11 (enkephalinase) activity in rat brain: cellular localization and codistribution with enkephalins in the globus pallidus. J. Neurosci. 9, 4439\u20134455 (1989).","journal-title":"J. Neurosci."},{"key":"BFnm1206_CR27","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1093\/oxfordjournals.jbchem.a022733","volume":"128","author":"J Takano","year":"2000","unstructured":"Takano, J., Watanabe, M., Hitomi, K. & Maki, M. Four types of calpastatin isoforms with distinct amino-terminal sequences are specified by alternative first exons and differentially expressed in mouse tissues. J. Biochem. 128, 83\u201392 (2000).","journal-title":"J. Biochem."},{"key":"BFnm1206_CR28","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/cne.10700","volume":"461","author":"S Jinno","year":"2003","unstructured":"Jinno, S. & Kosaka, T. Patterns of expression of neuropeptides in GABAergic nonprincipal neurons in the mouse hippocampus: Quantitative analysis with optical disector. J. Comp. Neurol. 461, 333\u2013349 (2003).","journal-title":"J. Comp. Neurol."},{"key":"BFnm1206_CR29","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1006\/meth.1999.0813","volume":"18","author":"G Wang","year":"1999","unstructured":"Wang, G. et al. Tyramide signal amplification method in multiple-label immunofluorescence confocal microscopy. Methods 18, 459\u2013464 (1999).","journal-title":"Methods"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm1206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm1206","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm1206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:18:17Z","timestamp":1684448297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm1206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,20]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,4]]}},"alternative-id":["BFnm1206"],"URL":"https:\/\/doi.org\/10.1038\/nm1206","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,20]]}}}