Biochemical Identification of the Neutral Endopeptidase Family Member Responsible for the Catabolism of Amyloid β Peptide in the Brain
Amyloid β peptide (Aβ) is a physiological peptide that is constantly catabolized in the brain. We previously demonstrated that an endopeptidase sensitive to phosphoramidon and thiorphan conducts the initial rate-limiting proteolysis of Aβ in vivo, but the exact molecular identity of the peptidase(s)...
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| Veröffentlicht in: | Journal of biochemistry (Tokyo) 2000-12, Vol.128 (6), p.897-902 |
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| container_title | Journal of biochemistry (Tokyo) |
| container_volume | 128 |
| creator | Takaki, Yoshie Iwata, Nobuhisa Tsubuki, Satoshi Taniguchi, Sayuri Toyoshima, Satoshi Lu, Bao Gerard, Norma P. Gerard, Craig Lee, Hahn-Jun Shirotani, Keiro Saido, Takaomi C. |
| description | Amyloid β peptide (Aβ) is a physiological peptide that is constantly catabolized in the brain. We previously demonstrated that an endopeptidase sensitive to phosphoramidon and thiorphan conducts the initial rate-limiting proteolysis of Aβ in vivo, but the exact molecular identity of the peptidase(s) has remained unknown because of the molecular redundancy of such activity. We analyzed the brain-derived enzyme by means of immuno-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the Aβ-degrading activity. Furthermore, kinetic analysis, giving a Km value of 2.8 ± 0.76 μM, indicated that Aβ1–42 is a relevant substrate for neprilysin. |
| doi_str_mv | 10.1093/oxfordjournals.jbchem.a022839 |
| format | Article |
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Furthermore, kinetic analysis, giving a Km value of 2.8 ± 0.76 μM, indicated that Aβ1–42 is a relevant substrate for neprilysin.</description><subject>Alzheimer's disease</subject><subject>Amino Acid Sequence</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>amyloid β</subject><subject>Animals</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>catabolism</subject><subject>Chromatography, Ion Exchange</subject><subject>Hydrolysis</subject><subject>Kinetics</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>neprilysin</subject><subject>Neprilysin - metabolism</subject><subject>neutral endopeptidase</subject><subject>peptide</subject><issn>0021-924X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1O5DAQhb1gBAzMFZA3sEuPHSdxZwkt_kQDIxhEi01UjsvCTRIH25HoE8x9OMicadINzKqq9L73VFWEHHI24awUP92bcV4v3eA7aMJkqepnbCfA0nQqyi2yy1jKkzLNFjvkewjL9ZgKsU12-GifcsF2yZ8T69YuW0NDLzV20Zqxj9Z11Bkan5He4BD9qJ522vXYR6shID2D1jYreo2tQk_vMPSuC1Y1SMedNr4ZRFCusaFdJx23q8ZZTf--01-bEKS223AnHmy3T76Z8Qb88Vn3yMPZ6e_ZRTK_Pb-cHc8TK_g0JlzVeWm0llIppgGgZAJQ8qxgvCwLpozIOa_rTJlMTwsmCjA1iswUNaQqlWKPHH3k9t69Dhhi1dpQY9NAh24IlUzznEnJRvDgExxUi7rqvW3Br6qv141A8gHYEPHtvw7-pSqkkHl1sXiqbp7mj7Pi6r5aiH8eFYgE</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>Takaki, Yoshie</creator><creator>Iwata, Nobuhisa</creator><creator>Tsubuki, Satoshi</creator><creator>Taniguchi, Sayuri</creator><creator>Toyoshima, Satoshi</creator><creator>Lu, Bao</creator><creator>Gerard, Norma P.</creator><creator>Gerard, Craig</creator><creator>Lee, Hahn-Jun</creator><creator>Shirotani, Keiro</creator><creator>Saido, Takaomi C.</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20001201</creationdate><title>Biochemical Identification of the Neutral Endopeptidase Family Member Responsible for the Catabolism of Amyloid β Peptide in the Brain</title><author>Takaki, Yoshie ; 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We previously demonstrated that an endopeptidase sensitive to phosphoramidon and thiorphan conducts the initial rate-limiting proteolysis of Aβ in vivo, but the exact molecular identity of the peptidase(s) has remained unknown because of the molecular redundancy of such activity. We analyzed the brain-derived enzyme by means of immuno-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the Aβ-degrading activity. Furthermore, kinetic analysis, giving a Km value of 2.8 ± 0.76 μM, indicated that Aβ1–42 is a relevant substrate for neprilysin.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>11098130</pmid><doi>10.1093/oxfordjournals.jbchem.a022839</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-924X |
| ispartof | Journal of biochemistry (Tokyo), 2000-12, Vol.128 (6), p.897-902 |
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| language | eng |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; Free Full-Text Journals in Chemistry |
| subjects | Alzheimer's disease Amino Acid Sequence Amyloid beta-Peptides - metabolism amyloid β Animals Brain - enzymology Brain - metabolism catabolism Chromatography, Ion Exchange Hydrolysis Kinetics Mice Molecular Sequence Data neprilysin Neprilysin - metabolism neutral endopeptidase peptide |
| title | Biochemical Identification of the Neutral Endopeptidase Family Member Responsible for the Catabolism of Amyloid β Peptide in the Brain |
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