Loading…
Developing β-secretase inhibitors for treatment of Alzheimer's disease
J. Neurochem. (2012) 120 (Suppl. 1), 71–83. β‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s...
Saved in:
| Published in: | Journal of neurochemistry 2012-01, Vol.120 (s1), p.71-83 |
|---|---|
| Main Authors: | , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433 |
| container_end_page | 83 |
| container_issue | s1 |
| container_start_page | 71 |
| container_title | Journal of neurochemistry |
| container_volume | 120 |
| creator | Ghosh, Arun K. Brindisi, Margherita Tang, Jordan |
| description | J. Neurochem. (2012) 120 (Suppl. 1), 71–83.
β‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β‐secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood‐brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β‐secretase inhibitor was shown to rescue age‐related cognitive decline in transgenic AD mice. A small number of β‐secretase inhibitors have also entered early phase clinical trials. These developments offer some optimism for the clinical development of a disease‐modifying drug for AD. |
| doi_str_mv | 10.1111/j.1471-4159.2011.07476.x |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3276244</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>920797468</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433</originalsourceid><addsrcrecordid>eNqNkd1u0zAYhi0EYmVwCygSBztK8L-dA5CmDjpQVU6Gdmg5yZfVJYmLnY6Oy-JCuCYcOirgBHxiS37eV5_9IJQRXJC0Xm4KwhXJORFlQTEhBVZcyWL_AM2OFw_RDGNKc4Y5PUFPYtxgTCSX5DE6oZRQKjWZocUF3ELnt264yb5_yyPUAUYbIXPD2lVu9CFmrQ_ZGMCOPQxj5tvsvPu6BtdDOItZ4yIk_il61NouwrP7_RR9fPvman6ZLz8s3s3Pl3ktOJE5k6UWWkmoGyXaxkKNtRacWgDAdcWqilOFbS00wZWgQmFJmlJrBhJDyxk7Ra8Pvdtd1UNTp4mC7cw2uN6GO-OtM3_eDG5tbvytYVRJynkqOLsvCP7zDuJoehdr6Do7gN9FU1KsSsWl_jdJBNOCMJXIF3-RG78LQ_oHQwXXUnCsSKL0gaqDjzFAe5yaYDNpNRsz2TOTPTNpNT-1mn2KPv_91cfgL48JeHUAvrgO7v672LxfzadTyueHvIsj7I95Gz4ZqZgS5nq1MOKalVeXamlW7AfhfcBk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2548654071</pqid></control><display><type>article</type><title>Developing β-secretase inhibitors for treatment of Alzheimer's disease</title><source>Wiley</source><source>Free Full-Text Journals in Chemistry</source><creator>Ghosh, Arun K. ; Brindisi, Margherita ; Tang, Jordan</creator><creatorcontrib>Ghosh, Arun K. ; Brindisi, Margherita ; Tang, Jordan</creatorcontrib><description>J. Neurochem. (2012) 120 (Suppl. 1), 71–83.
β‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β‐secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood‐brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β‐secretase inhibitor was shown to rescue age‐related cognitive decline in transgenic AD mice. A small number of β‐secretase inhibitors have also entered early phase clinical trials. These developments offer some optimism for the clinical development of a disease‐modifying drug for AD.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.2011.07476.x</identifier><identifier>PMID: 22122681</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alzheimer Disease - drug therapy ; Alzheimer Disease - enzymology ; Alzheimer's disease ; Amyloid precursor protein ; Amyloid Precursor Protein Secretases - antagonists & inhibitors ; Amyloid Precursor Protein Secretases - metabolism ; Animals ; BACE 1 ; beta-secretase ; Blood-brain barrier ; Brain ; Clinical trials ; Cognitive ability ; Drug Delivery Systems - methods ; Drug Delivery Systems - trends ; Drug development ; drugs ; Humans ; Inhibitors ; memapsin 2 ; Neurodegenerative diseases ; Pathogenesis ; Protease Inhibitors - chemical synthesis ; Protease Inhibitors - pharmacology ; Protease Inhibitors - therapeutic use ; Secretase ; Therapeutic targets ; Transgenic mice ; Treatment Outcome ; β-Site APP-cleaving enzymes</subject><ispartof>Journal of neurochemistry, 2012-01, Vol.120 (s1), p.71-83</ispartof><rights>2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry</rights><rights>2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.</rights><rights>Copyright Blackwell Publishing Ltd. Jan 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433</citedby><cites>FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22122681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghosh, Arun K.</creatorcontrib><creatorcontrib>Brindisi, Margherita</creatorcontrib><creatorcontrib>Tang, Jordan</creatorcontrib><title>Developing β-secretase inhibitors for treatment of Alzheimer's disease</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>J. Neurochem. (2012) 120 (Suppl. 1), 71–83.
β‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β‐secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood‐brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β‐secretase inhibitor was shown to rescue age‐related cognitive decline in transgenic AD mice. A small number of β‐secretase inhibitors have also entered early phase clinical trials. These developments offer some optimism for the clinical development of a disease‐modifying drug for AD.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - enzymology</subject><subject>Alzheimer's disease</subject><subject>Amyloid precursor protein</subject><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Animals</subject><subject>BACE 1</subject><subject>beta-secretase</subject><subject>Blood-brain barrier</subject><subject>Brain</subject><subject>Clinical trials</subject><subject>Cognitive ability</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Delivery Systems - trends</subject><subject>Drug development</subject><subject>drugs</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>memapsin 2</subject><subject>Neurodegenerative diseases</subject><subject>Pathogenesis</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Protease Inhibitors - therapeutic use</subject><subject>Secretase</subject><subject>Therapeutic targets</subject><subject>Transgenic mice</subject><subject>Treatment Outcome</subject><subject>β-Site APP-cleaving enzymes</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkd1u0zAYhi0EYmVwCygSBztK8L-dA5CmDjpQVU6Gdmg5yZfVJYmLnY6Oy-JCuCYcOirgBHxiS37eV5_9IJQRXJC0Xm4KwhXJORFlQTEhBVZcyWL_AM2OFw_RDGNKc4Y5PUFPYtxgTCSX5DE6oZRQKjWZocUF3ELnt264yb5_yyPUAUYbIXPD2lVu9CFmrQ_ZGMCOPQxj5tvsvPu6BtdDOItZ4yIk_il61NouwrP7_RR9fPvman6ZLz8s3s3Pl3ktOJE5k6UWWkmoGyXaxkKNtRacWgDAdcWqilOFbS00wZWgQmFJmlJrBhJDyxk7Ra8Pvdtd1UNTp4mC7cw2uN6GO-OtM3_eDG5tbvytYVRJynkqOLsvCP7zDuJoehdr6Do7gN9FU1KsSsWl_jdJBNOCMJXIF3-RG78LQ_oHQwXXUnCsSKL0gaqDjzFAe5yaYDNpNRsz2TOTPTNpNT-1mn2KPv_91cfgL48JeHUAvrgO7v672LxfzadTyueHvIsj7I95Gz4ZqZgS5nq1MOKalVeXamlW7AfhfcBk</recordid><startdate>201201</startdate><enddate>201201</enddate><creator>Ghosh, Arun K.</creator><creator>Brindisi, Margherita</creator><creator>Tang, Jordan</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201201</creationdate><title>Developing β-secretase inhibitors for treatment of Alzheimer's disease</title><author>Ghosh, Arun K. ; Brindisi, Margherita ; Tang, Jordan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - enzymology</topic><topic>Alzheimer's disease</topic><topic>Amyloid precursor protein</topic><topic>Amyloid Precursor Protein Secretases - antagonists & inhibitors</topic><topic>Amyloid Precursor Protein Secretases - metabolism</topic><topic>Animals</topic><topic>BACE 1</topic><topic>beta-secretase</topic><topic>Blood-brain barrier</topic><topic>Brain</topic><topic>Clinical trials</topic><topic>Cognitive ability</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug Delivery Systems - trends</topic><topic>Drug development</topic><topic>drugs</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>memapsin 2</topic><topic>Neurodegenerative diseases</topic><topic>Pathogenesis</topic><topic>Protease Inhibitors - chemical synthesis</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Protease Inhibitors - therapeutic use</topic><topic>Secretase</topic><topic>Therapeutic targets</topic><topic>Transgenic mice</topic><topic>Treatment Outcome</topic><topic>β-Site APP-cleaving enzymes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghosh, Arun K.</creatorcontrib><creatorcontrib>Brindisi, Margherita</creatorcontrib><creatorcontrib>Tang, Jordan</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosh, Arun K.</au><au>Brindisi, Margherita</au><au>Tang, Jordan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Developing β-secretase inhibitors for treatment of Alzheimer's disease</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2012-01</date><risdate>2012</risdate><volume>120</volume><issue>s1</issue><spage>71</spage><epage>83</epage><pages>71-83</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>J. Neurochem. (2012) 120 (Suppl. 1), 71–83.
β‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor drugs. During the past decade, steady progress has been made in the evolution of β‐secretase inhibitors toward better drug properties. Recent inhibitors are potent, selective and have been shown to penetrate the blood‐brain barrier to inhibit Aβ levels in the brains of experimental animals. Moreover, continuous administration of a β‐secretase inhibitor was shown to rescue age‐related cognitive decline in transgenic AD mice. A small number of β‐secretase inhibitors have also entered early phase clinical trials. These developments offer some optimism for the clinical development of a disease‐modifying drug for AD.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22122681</pmid><doi>10.1111/j.1471-4159.2011.07476.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3042 |
| ispartof | Journal of neurochemistry, 2012-01, Vol.120 (s1), p.71-83 |
| issn | 0022-3042 1471-4159 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3276244 |
| source | Wiley; Free Full-Text Journals in Chemistry |
| subjects | Alzheimer Disease - drug therapy Alzheimer Disease - enzymology Alzheimer's disease Amyloid precursor protein Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism Animals BACE 1 beta-secretase Blood-brain barrier Brain Clinical trials Cognitive ability Drug Delivery Systems - methods Drug Delivery Systems - trends Drug development drugs Humans Inhibitors memapsin 2 Neurodegenerative diseases Pathogenesis Protease Inhibitors - chemical synthesis Protease Inhibitors - pharmacology Protease Inhibitors - therapeutic use Secretase Therapeutic targets Transgenic mice Treatment Outcome β-Site APP-cleaving enzymes |
| title | Developing β-secretase inhibitors for treatment of Alzheimer's disease |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T22%3A30%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Developing%20%CE%B2-secretase%20inhibitors%20for%20treatment%20of%20Alzheimer's%20disease&rft.jtitle=Journal%20of%20neurochemistry&rft.au=Ghosh,%20Arun%20K.&rft.date=2012-01&rft.volume=120&rft.issue=s1&rft.spage=71&rft.epage=83&rft.pages=71-83&rft.issn=0022-3042&rft.eissn=1471-4159&rft_id=info:doi/10.1111/j.1471-4159.2011.07476.x&rft_dat=%3Cproquest_pubme%3E920797468%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5416-36985876ecd75fdaec088542aeee0cb3bb4270ac5810b5257061d9883e60ef433%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2548654071&rft_id=info:pmid/22122681&rfr_iscdi=true |