Nature Reviews Drug Discovery 2012.06.pdf

《Nature Reviews Drug Discovery 2012.06.pdf》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、INTHISISSUEhefindingthatcaloricrestrictionslowsageinganddelaysdiseaseonsetinseveralspecieshasstimulatedinterestinunderstandingTthemolecularmechanismsunderlyingthesebeneficialeffectsandindevelopingpharmacologicalagentsthatarecapableofmimickingsuchdietaryintervention.Oneofthemo

2、stintriguingmoleculestoemergefromsuchstudiesistheNAD-dependentdeacetylasesirtuin1(SIRT1),whichisthoughttohavearoleinage-relatedconditionsincludingdiabetes,cardiovasculardisease,neurodegenerativedisordersandcancer.NPGBaurandcolleaguesdiscusssomeoftheserolesandthepotentialofSir

3、tuinsastherapeutictargetsp443SIRT1asadrugtarget,includingtherecentcontroversiessurroundingthemechanismofactionofSIRT1activators.Fragmentedunderstandingofthemechanismsofmetastasis—whichisresponsibleformostofthedeathsfromsolidcancers—hashamperedtheidentificationofdrugswithanti-

4、metastaticefficacy.However,substantialprogresshasbeenrecentlymadeinthedevelopmentofpreclinicalmodelsandtheidentificationofgenesthatregulatemetastasisoractasbiomarkers.Focusingonbreastcancer,Andersonandcolleaguesdiscusshowsuchknowledgecouldbeappliedinthediscoveryanddevelopment

5、ofnovelanti-metastatictherapies.KnowledgeofrelevantbiomarkerscouldhelpaddresstheheterogeneityPhotodisc/GettyNeuropeptidereceptorsandamongpatientsinclinicaltrialsforpsychiatricdiseasessuchasdepressionpsychiatricdiseasesp462andschizophrenia;thishasbeenamajorfactorinthefailureof

6、effortstodevelopnoveldrugstargetingvariousneuropeptidereceptors.ThisisdiscussedbyGriebelandHolsboer,whoanalysethediscrepancybetweenthehighlypromisingpreclinicaldataandtheunsuccessfulclinicaltrialsforseveralclassesofneuropeptidereceptormodulators,suggestingnewwaystoexploitthei

7、rfullpotential.EDITORIALOFFICEMAnAgingproductioneditor:JudithShadwellEDITORSLondonNatureReviews@nature.comSeniorproductioneditor:SimonFenwickTheMacmillanBuilding,4CrinanStreet,productioncontroLLer:NatalieSmithLondonN19XW,UKSenioreditoriALASSiStAnt:LauraCornsTel:+44(0)20784336

8、20;editoriALASSiStAnt:EllaLinesFax:+44(0)2078433629webproductionMAnA