Butyrylcholinesterase: An Important New Target in Alzheimer's Disease Therapy
Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remain...
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| Veröffentlicht in: | International psychogeriatrics 2002-02, Vol.14 (S1), p.77-91 |
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| description | Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options. |
| doi_str_mv | 10.1017/S1041610203008676 |
| format | Article |
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However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options.</description><identifier>ISSN: 1041-6102</identifier><identifier>EISSN: 1741-203X</identifier><identifier>DOI: 10.1017/S1041610203008676</identifier><identifier>PMID: 12636181</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Acetylcholine - metabolism ; Acetylcholinesterase ; Acetylcholinesterase - physiology ; Alzheimer Disease - diagnosis ; Alzheimer Disease - drug therapy ; Alzheimer Disease - enzymology ; Alzheimer Disease - psychology ; Alzheimer's disease ; beta-amyloid ; Brain - drug effects ; Brain - enzymology ; butyrylcholinesterase ; Butyrylcholinesterase - physiology ; cholinesterase inhibitor ; Cholinesterase Inhibitors - adverse effects ; Cholinesterase Inhibitors - therapeutic use ; cymserine ; Disease Models, Animal ; donepezil ; Enzyme inhibitors ; Enzymes ; galantamine ; Humans ; rivastigmine ; tacrine ; Treatment Outcome</subject><ispartof>International psychogeriatrics, 2002-02, Vol.14 (S1), p.77-91</ispartof><rights>2002 International Psychogeriatric Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-1c782cf751cbeaed5dca81b923d53ced6be9d16e4fd88895694e56d8dcfc41e53</citedby><cites>FETCH-LOGICAL-c469t-1c782cf751cbeaed5dca81b923d53ced6be9d16e4fd88895694e56d8dcfc41e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S1041610203008676/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,314,776,780,12825,27901,27902,30976,55603</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12636181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Greig, Nigel H.</creatorcontrib><creatorcontrib>Lahiri, Debomoy K.</creatorcontrib><creatorcontrib>Sambamurti, Kumar</creatorcontrib><title>Butyrylcholinesterase: An Important New Target in Alzheimer's Disease Therapy</title><title>International psychogeriatrics</title><addtitle>Int. Psychogeriatr</addtitle><description>Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options.</description><subject>Acetylcholine - metabolism</subject><subject>Acetylcholinesterase</subject><subject>Acetylcholinesterase - physiology</subject><subject>Alzheimer Disease - diagnosis</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - enzymology</subject><subject>Alzheimer Disease - psychology</subject><subject>Alzheimer's disease</subject><subject>beta-amyloid</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>butyrylcholinesterase</subject><subject>Butyrylcholinesterase - physiology</subject><subject>cholinesterase inhibitor</subject><subject>Cholinesterase Inhibitors - adverse effects</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>cymserine</subject><subject>Disease Models, Animal</subject><subject>donepezil</subject><subject>Enzyme inhibitors</subject><subject>Enzymes</subject><subject>galantamine</subject><subject>Humans</subject><subject>rivastigmine</subject><subject>tacrine</subject><subject>Treatment Outcome</subject><issn>1041-6102</issn><issn>1741-203X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>7QJ</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kEtr3DAUhUVJSaZJfkA3xRBIV250bVmWm9V0-shAHotMoTshS9cZDX5MJLvF-fXVMIaWhmali-53DuceQt4C_QAU8ot7oAw40ISmlAqe81dkBjmDOHz8OAhzWMe7_RF54_2G0iRLgR2SI0h4ykHAjNx8GvrRjbVed7Vt0ffolMeP0byNls22c71q--gWf0Ur5R6wj2wbzeunNdoG3XsffbYeAx-t1kG3HU_I60rVHk-n95h8__pltbiKr---LRfz61gzXvQx6Fwkusoz0CUqNJnRSkBZJKnJUo2Gl1gY4MgqI4QoMl4wzLgRRleaAWbpMTnf-25d9ziE1LKxXmNdqxa7wcs8ETxcygJ49g-46QbXhmwSigKoYFzs7GBPadd577CSW2cb5UYJVO6als-aDpp3k_NQNmj-KKZqA3C5BzAU8dOik15bbMN51qHupensi_bpFEk1pbPmAf9K_l_Vb5pqmn8</recordid><startdate>20020201</startdate><enddate>20020201</enddate><creator>Greig, Nigel H.</creator><creator>Lahiri, Debomoy K.</creator><creator>Sambamurti, Kumar</creator><general>Cambridge University Press</general><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>0-V</scope><scope>3V.</scope><scope>7QJ</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88J</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HEHIP</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2R</scope><scope>M2S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20020201</creationdate><title>Butyrylcholinesterase: An Important New Target in Alzheimer's Disease Therapy</title><author>Greig, Nigel H. ; Lahiri, Debomoy K. ; Sambamurti, Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-1c782cf751cbeaed5dca81b923d53ced6be9d16e4fd88895694e56d8dcfc41e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Acetylcholine - metabolism</topic><topic>Acetylcholinesterase</topic><topic>Acetylcholinesterase - physiology</topic><topic>Alzheimer Disease - diagnosis</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - enzymology</topic><topic>Alzheimer Disease - psychology</topic><topic>Alzheimer's disease</topic><topic>beta-amyloid</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>butyrylcholinesterase</topic><topic>Butyrylcholinesterase - physiology</topic><topic>cholinesterase inhibitor</topic><topic>Cholinesterase Inhibitors - adverse effects</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>cymserine</topic><topic>Disease Models, Animal</topic><topic>donepezil</topic><topic>Enzyme inhibitors</topic><topic>Enzymes</topic><topic>galantamine</topic><topic>Humans</topic><topic>rivastigmine</topic><topic>tacrine</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Greig, Nigel H.</creatorcontrib><creatorcontrib>Lahiri, Debomoy K.</creatorcontrib><creatorcontrib>Sambamurti, Kumar</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Social Science Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Sociology Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Social Science Database</collection><collection>Sociology Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>International psychogeriatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Greig, Nigel H.</au><au>Lahiri, Debomoy K.</au><au>Sambamurti, Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Butyrylcholinesterase: An Important New Target in Alzheimer's Disease Therapy</atitle><jtitle>International psychogeriatrics</jtitle><addtitle>Int. 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Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>12636181</pmid><doi>10.1017/S1041610203008676</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | Applied Social Sciences Index & Abstracts (ASSIA); MEDLINE; Cambridge University Press Journals Complete |
| subjects | Acetylcholine - metabolism Acetylcholinesterase Acetylcholinesterase - physiology Alzheimer Disease - diagnosis Alzheimer Disease - drug therapy Alzheimer Disease - enzymology Alzheimer Disease - psychology Alzheimer's disease beta-amyloid Brain - drug effects Brain - enzymology butyrylcholinesterase Butyrylcholinesterase - physiology cholinesterase inhibitor Cholinesterase Inhibitors - adverse effects Cholinesterase Inhibitors - therapeutic use cymserine Disease Models, Animal donepezil Enzyme inhibitors Enzymes galantamine Humans rivastigmine tacrine Treatment Outcome |
| title | Butyrylcholinesterase: An Important New Target in Alzheimer's Disease Therapy |
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