000282551 001__ 282551
000282551 005__ 20251218103441.0
000282551 0247_ $$2doi$$a10.1186/s12974-025-03616-y
000282551 0247_ $$2pmid$$apmid:41291747
000282551 0247_ $$2pmc$$apmc:PMC12648879
000282551 037__ $$aDZNE-2025-01314
000282551 041__ $$aEnglish
000282551 082__ $$a610
000282551 1001_ $$aBrunialti, Electra$$b0
000282551 245__ $$aMetabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.
000282551 260__ $$aLondon$$bBioMed Central$$c2025
000282551 3367_ $$2DRIVER$$aarticle
000282551 3367_ $$2DataCite$$aOutput Types/Journal article
000282551 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1764680019_28229
000282551 3367_ $$2BibTeX$$aARTICLE
000282551 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000282551 3367_ $$00$$2EndNote$$aJournal Article
000282551 520__ $$aMutations in the GBA gene, which reduce β-glucocerebrosidase (GCase) activity, represent the most significant genetic risk factor for Parkinson’s disease (PD). Decreased GCase activity has also been observed in sporadic PD cases, supporting a broader role for GCase in the poorly understood mechanisms underlying PD etiopathogenesis. While most studies on the relationship between GBA mutations and PD have focused on neurons, evidence suggests that PD pathology promoted by GCase deficiency involves other cell types and, in particular, interactions between neuronal and glial cells. Here, we identify microglia as primary players undergoing significant alterations at early stages of the pathological processes triggered by a GCase impairment. Using both pharmacological and genetic mouse models of GCase deficiency, we observed microglial morphological, transcriptional and metabolic changes. Interestingly, these changes were associated with a cell-specific, significant reduction of microglial ATP levels. When microglial ATP depletion was reproduced in an in vitro system of co-cultured microglial and neuronal cells, the neuroprotective properties of microglia were compromised, resulting in reduced cytoprotective and detoxifying pathways in neurons. These findings underscore the role of microglia in PD pathogenesis and point to a pathogenetic mechanism by which microglial metabolic disturbances leading to ATP depletion enhance neuronal vulnerability to injury and neurodegeneration. This mechanism could be targeted for therapeutic intervention aimed at mitigating PD risk and counteracting the development of PD pathology.The online version contains supplementary material available at 10.1186/s12974-025-03616-y.
000282551 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000282551 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000282551 650_7 $$2Other$$aATP
000282551 650_7 $$2Other$$aEnergetic failure
000282551 650_7 $$2Other$$aGaucher’s disease
000282551 650_7 $$2Other$$aMicroglia
000282551 650_7 $$2Other$$aNeuroprotection
000282551 650_7 $$2Other$$aParkinson’s disease
000282551 7001_ $$aVilla, Alessandro$$b1
000282551 7001_ $$0P:(DE-2719)9002553$$aSzego, Eva M$$b2$$udzne
000282551 7001_ $$0P:(DE-2719)9001592$$aLa Vitola, Pietro$$b3$$udzne
000282551 7001_ $$aDrago, Denise$$b4
000282551 7001_ $$aPavlovic, Radmila$$b5
000282551 7001_ $$aFontana, Laura$$b6
000282551 7001_ $$aTuna, Doga$$b7
000282551 7001_ $$aPanzeri, Alessia$$b8
000282551 7001_ $$aMeda, Clara$$b9
000282551 7001_ $$0P:(DE-2719)9001801$$aWeissleder, Christin$$b10$$udzne
000282551 7001_ $$aRondinone, Ornella$$b11
000282551 7001_ $$aPitasi, Mattia$$b12
000282551 7001_ $$aMiozzo, Monica$$b13
000282551 7001_ $$0P:(DE-2719)2810385$$aDeleidi, Michela$$b14$$udzne
000282551 7001_ $$aAndolfo, Annapaola$$b15
000282551 7001_ $$0P:(DE-2719)2481741$$aDi Monte, Donato A$$b16$$udzne
000282551 7001_ $$aCiana, Paolo$$b17
000282551 773__ $$0PERI:(DE-600)2156455-3$$a10.1186/s12974-025-03616-y$$gVol. 22, no. 1, p. 279$$n1$$p279$$tJournal of neuroinflammation$$v22$$x1742-2094$$y2025
000282551 8564_ $$uhttps://pub.dzne.de/record/282551/files/DZNE-2025-01314.pdf$$yOpenAccess
000282551 8564_ $$uhttps://pub.dzne.de/record/282551/files/DZNE-2025-01314.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000282551 909CO $$ooai:pub.dzne.de:282551$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000282551 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002553$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000282551 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001592$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000282551 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9001801$$aExternal Institute$$b10$$kExtern
000282551 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2810385$$aExternal Institute$$b14$$kExtern
000282551 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2481741$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b16$$kDZNE
000282551 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
000282551 9141_ $$y2025
000282551 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000282551 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ NEUROINFLAMM : 2022$$d2024-12-16
000282551 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000282551 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-04-10T15:42:04Z
000282551 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-04-10T15:42:04Z
000282551 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bJ NEUROINFLAMM : 2022$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-16
000282551 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-16
000282551 9201_ $$0I:(DE-2719)1013008$$kAG Di Monte$$lNeurodegeneration and Neuroprotection in Parkinson´s Disease$$x0
000282551 980__ $$ajournal
000282551 980__ $$aVDB
000282551 980__ $$aUNRESTRICTED
000282551 980__ $$aI:(DE-2719)1013008
000282551 9801_ $$aFullTexts