000155465 001__ 155465
000155465 005__ 20240320115509.0
000155465 0247_ $$2pmc$$apmc:PMC8457068
000155465 0247_ $$2doi$$a10.1111/bph.15515
000155465 0247_ $$2pmid$$apmid:33931856
000155465 0247_ $$2ISSN$$a0007-1188
000155465 0247_ $$2ISSN$$a0366-0826
000155465 0247_ $$2ISSN$$a1476-5381
000155465 0247_ $$2ISSN$$a2056-8177
000155465 0247_ $$2altmetric$$aaltmetric:105464755
000155465 037__ $$aDZNE-2021-00664
000155465 041__ $$aEnglish
000155465 082__ $$a610
000155465 1001_ $$aMilanese, Marco$$b0
000155465 245__ $$aBlocking glutamate mGlu5 receptors with the negative allosteric modulator CTEP improves disease course in SOD1G93A mouse model of amyotrophic lateral sclerosis.
000155465 260__ $$aMalden, MA$$bWiley$$c2021
000155465 3367_ $$2DRIVER$$aarticle
000155465 3367_ $$2DataCite$$aOutput Types/Journal article
000155465 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1636452650_20945
000155465 3367_ $$2BibTeX$$aARTICLE
000155465 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000155465 3367_ $$00$$2EndNote$$aJournal Article
000155465 520__ $$aThe pathogenesis of amyotrophic lateral sclerosis (ALS) is not fully clarified, although excessive glutamate (Glu) transmission and the downstream cytotoxic cascades are major mechanisms for motor neuron death. Two metabotropic glutamate receptors (mGlu1 and mGlu5 ) are overexpressed in ALS and regulate cellular disease processes. Expression and function of mGlu5 receptors are altered at early symptomatic stages in the SOD1G93A mouse model of ALS and knockdown of mGlu5 receptors in SOD1G93A mice improved disease progression.We treated male and female SOD1G93A mice with 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP), an orally available mGlu5 receptor negative allosteric modulator (NAM), using doses of 2 mg·kg-1 per 48 h or 4 mg·kg-1 per 24 h from Day 90, an early symptomatic disease stage. Disease progression was studied by behavioural and histological approaches.CTEP dose-dependently ameliorated clinical features in SOD1G93A mice. The lower dose increased survival and improved motor skills in female mice, with barely positive effects in male mice. Higher doses significantly ameliorated disease symptoms and survival in both males and females, females being more responsive. CTEP also reduced motor neuron death, astrocyte and microglia activation, and abnormal glutamate release in the spinal cord, with equal effects in male and female mice. No differences were also observed in CTEP access to the brain.Our results suggest that mGlu5 receptors are promising targets for the treatment of ALS and highlight mGlu5 receptor NAMs as effective pharmacological tools with translational potential.
000155465 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000155465 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000155465 650_7 $$2Other$$a2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP)
000155465 650_7 $$2Other$$aSOD1G93A mice
000155465 650_7 $$2Other$$aamyotrophic lateral sclerosis (ALS)
000155465 650_7 $$2Other$$ain vivo pharmacological treatment
000155465 650_7 $$2Other$$ametabotropic glutamate receptor 5 (mGlu5 receptor)
000155465 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: drug therapy
000155465 650_2 $$2MeSH$$aAnimals
000155465 650_2 $$2MeSH$$aDisease Models, Animal
000155465 650_2 $$2MeSH$$aDisease Progression
000155465 650_2 $$2MeSH$$aFemale
000155465 650_2 $$2MeSH$$aGlutamic Acid
000155465 650_2 $$2MeSH$$aMale
000155465 650_2 $$2MeSH$$aMice
000155465 650_2 $$2MeSH$$aMice, Transgenic
000155465 650_2 $$2MeSH$$aReceptor, Metabotropic Glutamate 5
000155465 650_2 $$2MeSH$$aSpinal Cord
000155465 650_2 $$2MeSH$$aSuperoxide Dismutase
000155465 650_2 $$2MeSH$$aSuperoxide Dismutase-1: genetics
000155465 7001_ $$aBonifacino, Tiziana$$b1
000155465 7001_ $$aTorazza, Carola$$b2
000155465 7001_ $$0P:(DE-2719)9000707$$aProvenzano, Francesca$$b3$$udzne
000155465 7001_ $$aKumar, Mandeep$$b4
000155465 7001_ $$aRavera, Silvia$$b5
000155465 7001_ $$aZerbo, Arianna Roberta$$b6
000155465 7001_ $$aFrumento, Giulia$$b7
000155465 7001_ $$aBalbi, Matilde$$b8
000155465 7001_ $$0P:(DE-2719)2812645$$aNguyen, Quynh Tram Julia$$b9$$udzne
000155465 7001_ $$aBertola, Nadia$$b10
000155465 7001_ $$aFerrando, Sara$$b11
000155465 7001_ $$aViale, Maurizio$$b12
000155465 7001_ $$aProfumo, Aldo$$b13
000155465 7001_ $$0P:(DE-HGF)0$$aBonanno, Giambattista$$b14$$eCorresponding author
000155465 773__ $$0PERI:(DE-600)2029728-2$$a10.1111/bph.15515$$gp. bph.15515$$n18$$p3747-3764$$tBritish journal of pharmacology$$v178$$x1476-5381$$y2021
000155465 8564_ $$uhttps://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15515
000155465 8564_ $$uhttps://pub.dzne.de/record/155465/files/19541.pdf$$yOpenAccess
000155465 8564_ $$uhttps://pub.dzne.de/record/155465/files/19541.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000155465 909CO $$ooai:pub.dzne.de:155465$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000155465 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000707$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000155465 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2812645$$aExternal Institute$$b9$$kExtern
000155465 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000155465 9130_ $$0G:(DE-HGF)POF3-341$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vMolecular Signaling$$x0
000155465 9141_ $$y2021
000155465 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-02
000155465 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBRIT J PHARMACOL : 2021$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2021-02-02$$wger
000155465 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-02
000155465 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000155465 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bBRIT J PHARMACOL : 2021$$d2022-11-23
000155465 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-02
000155465 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000155465 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-23
000155465 9201_ $$0I:(DE-2719)1210011$$kAG Deleidi$$lMitochondria and inflammation in neurodegeneration$$x0
000155465 980__ $$ajournal
000155465 980__ $$aVDB
000155465 980__ $$aUNRESTRICTED
000155465 980__ $$aI:(DE-2719)1210011
000155465 9801_ $$aFullTexts