000155693 001__ 155693
000155693 005__ 20240227115125.0
000155693 0247_ $$2doi$$a10.15252/emmm.202013131
000155693 0247_ $$2pmid$$apmid:34125498
000155693 0247_ $$2pmc$$apmc:PMC8261490
000155693 0247_ $$2ISSN$$a1715-4684
000155693 0247_ $$2ISSN$$a1757-4676
000155693 0247_ $$2ISSN$$a1757-4684
000155693 0247_ $$2altmetric$$aaltmetric:107613592
000155693 037__ $$aDZNE-2021-00861
000155693 041__ $$aEnglish
000155693 082__ $$a610
000155693 1001_ $$0P:(DE-HGF)0$$aCatanese, Alberto$$b0
000155693 245__ $$aSynaptic disruption and CREB-regulated transcription are restored by K+ channel blockers in ALS.
000155693 260__ $$aHeidelberg$$bEMBO Press$$c2021
000155693 3367_ $$2DRIVER$$aarticle
000155693 3367_ $$2DataCite$$aOutput Types/Journal article
000155693 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1709022555_12959
000155693 3367_ $$2BibTeX$$aARTICLE
000155693 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000155693 3367_ $$00$$2EndNote$$aJournal Article
000155693 520__ $$aAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is still missing effective therapeutic strategies. Although manipulation of neuronal excitability has been tested in murine and human ALS models, it is still under debate whether neuronal activity might represent a valid target for efficient therapies. In this study, we exploited a combination of transcriptomics, proteomics, optogenetics and pharmacological approaches to investigate the activity-related pathological features of iPSC-derived C9orf72-mutant motoneurons (MN). We found that human ALSC9orf72 MN are characterized by accumulation of aberrant aggresomes, reduced expression of synaptic genes, loss of synaptic contacts and a dynamic 'malactivation' of the transcription factor CREB. A similar phenotype was also found in TBK1-mutant MN and upon overexpression of poly(GA) aggregates in primary neurons, indicating a strong convergence of pathological phenotypes on synaptic dysregulation. Notably, these alterations, along with neuronal survival, could be rescued by treating ALS-related neurons with the K+ channel blockers Apamin and XE991, which, respectively, target the SK and the Kv7 channels. Thus, our study shows that restoring the activity-dependent transcriptional programme and synaptic composition exerts a neuroprotective effect on ALS disease progression.
000155693 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000155693 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x1
000155693 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000155693 650_7 $$2Other$$aALS
000155693 650_7 $$2Other$$aCREB
000155693 650_7 $$2Other$$ahiPSC
000155693 650_7 $$2Other$$amotoneuron
000155693 650_7 $$2Other$$asynapse
000155693 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: drug therapy
000155693 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000155693 650_2 $$2MeSH$$aAnimals
000155693 650_2 $$2MeSH$$aHumans
000155693 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells
000155693 650_2 $$2MeSH$$aMice
000155693 650_2 $$2MeSH$$aMotor Neurons
000155693 650_2 $$2MeSH$$aNeurodegenerative Diseases
000155693 650_2 $$2MeSH$$aNeuroprotective Agents
000155693 7001_ $$0P:(DE-HGF)0$$aRajkumar, Sandeep$$b1
000155693 7001_ $$aSommer, Daniel$$b2
000155693 7001_ $$aFreisem, Dennis$$b3
000155693 7001_ $$aWirth, Alexander$$b4
000155693 7001_ $$aAly, Amr$$b5
000155693 7001_ $$0P:(DE-2719)9000658$$aMassa-López, David$$b6$$udzne
000155693 7001_ $$aOlivieri, Andrea$$b7
000155693 7001_ $$aTorelli, Federica$$b8
000155693 7001_ $$aIoannidis, Valentin$$b9
000155693 7001_ $$aLipecka, Joanna$$b10
000155693 7001_ $$aGuerrera, Ida Chiara$$b11
000155693 7001_ $$0P:(DE-HGF)0$$aZytnicki, Daniel$$b12
000155693 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert$$b13$$udzne
000155693 7001_ $$0P:(DE-HGF)0$$aKabashi, Edor$$b14
000155693 7001_ $$aMulaw, Medhanie A$$b15
000155693 7001_ $$0P:(DE-2719)2812851$$aRoselli, Francesco$$b16$$udzne
000155693 7001_ $$0P:(DE-2719)2812855$$aBöckers, Tobias$$b17$$eLast author$$udzne
000155693 773__ $$0PERI:(DE-600)2485479-7$$a10.15252/emmm.202013131$$gVol. 13, no. 7$$n7$$pe13131$$tEMBO molecular medicine$$v13$$x1757-4684$$y2021
000155693 8564_ $$uhttps://pub.dzne.de/record/155693/files/DZNE-2021-00861.pdf$$yOpenAccess
000155693 8564_ $$uhttps://pub.dzne.de/record/155693/files/DZNE-2021-00861.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000155693 909CO $$ooai:pub.dzne.de:155693$$pVDB$$popen_access$$pdnbdelivery$$pdriver$$popenaire
000155693 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000658$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b6$$kDZNE
000155693 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812633$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000155693 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812851$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b16$$kDZNE
000155693 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812855$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b17$$kDZNE
000155693 9131_ $$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$$x0
000155693 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x1
000155693 9130_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0
000155693 9130_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x1
000155693 9141_ $$y2021
000155693 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-04
000155693 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000155693 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bEMBO MOL MED : 2021$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bEMBO MOL MED : 2021$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-07-19T13:19:31Z
000155693 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-04
000155693 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-07-19T13:19:31Z
000155693 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-29
000155693 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000155693 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review, Double blind peer review$$d2021-07-19T13:19:31Z
000155693 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2021-02-04
000155693 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-04
000155693 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2021-02-04
000155693 9201_ $$0I:(DE-2719)5000077$$kClinical Study Center Ulm$$lClinical Study Center Ulm$$x0
000155693 9201_ $$0I:(DE-2719)1910001$$kAG Roselli$$lMetabolic Changes in Neurodegeneration$$x1
000155693 9201_ $$0I:(DE-2719)1910002$$kAG Böckers$$lTranslational Protein Biochemistry$$x2
000155693 980__ $$ajournal
000155693 980__ $$aVDB
000155693 980__ $$aI:(DE-2719)5000077
000155693 980__ $$aI:(DE-2719)1910001
000155693 980__ $$aI:(DE-2719)1910002
000155693 980__ $$aUNRESTRICTED
000155693 9801_ $$aFullTexts