Matches in SemOpenAlex for { <https://semopenalex.org/work/W3198662016> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W3198662016 abstract "<h3>Background</h3> Cholesterol is a multifaceted molecule essential for brain function (Martin 2014). In the adult brain, cholesterol is produced locally by astrocytes and transferred to neurons through apoE-containing lipoproteins (Jurevics & Morell 1995; Mauch 2001). Disruption of brain cholesterol pathways has been linked to several neurological disorders, including Huntington’s disease (HD), a genetic, neurodegenerative disorder caused by a CAG expansion in the gene encoding the Huntingtin protein (Valenza & Cattaneo 2011). Brain cholesterol biosynthesis and content are reduced in several HD models (Valenza 2005; 2007; 2010; Shankaran 2017). The underlying molecular mechanism relies on reduced nuclear translocation of SREBP2, the transcription factor that controls the transcription of several genes involved in cholesterol biosynthesis (Valenza 2015; Di Pardo 2020). We have recently shown that cholesterol supplementation to the brain, with different delivery systems, ameliorates synaptic and behavioral defects in the R6/2 mouse model (Valenza 2015; Birolini 2020; Birolini 2021). <h3>Aims and Methods</h3> Here, we used recombinant adeno-associated virus 2/5 to deliver exogenous SREBP2 specifically in astrocytes in order to enhance the endogenous cholesterol biosynthesis in the striatum of R6/2 mice. <h3>Results</h3> We found that exogenous SREBP2 stimulates the transcription of key cholesterol biosynthesis genes resulting in fully restoration of synaptic transmission, reversal of Drd2 transcript levels, clearance of mutant Huntingtin (muHTT) aggregates and rescue of behavioral deficits. <h3>Conclusions</h3> These results demonstrate that stimulating cholesterol biosynthesis in striatal astrocytes has a positive effect on behavioral decline and disease-related phenotypes in HD mice. Furthermore, we have demonstrated that glial SREBP2 participates in HD pathogenesis in vivo, highlighting the translational potential of cholesterol-based strategies for this disease." @default.
- W3198662016 created "2021-09-13" @default.
- W3198662016 creator A5000410225 @default.
- W3198662016 creator A5013719514 @default.
- W3198662016 creator A5034637504 @default.
- W3198662016 creator A5038230299 @default.
- W3198662016 creator A5039256755 @default.
- W3198662016 creator A5039534612 @default.
- W3198662016 creator A5044458859 @default.
- W3198662016 creator A5061201309 @default.
- W3198662016 creator A5063266121 @default.
- W3198662016 creator A5064191727 @default.
- W3198662016 creator A5081553465 @default.
- W3198662016 creator A5081819845 @default.
- W3198662016 creator A5087588860 @default.
- W3198662016 creator A5089345009 @default.
- W3198662016 creator A5090106620 @default.
- W3198662016 date "2021-09-01" @default.
- W3198662016 modified "2023-10-18" @default.
- W3198662016 title "I06 SREBP2 delivery to striatal astrocytes normalizes transcription of cholesterol biosynthesis genes and ameliorates pathological features in huntington’s disease" @default.
- W3198662016 doi "https://doi.org/10.1136/jnnp-2021-ehdn.120" @default.
- W3198662016 hasPublicationYear "2021" @default.
- W3198662016 type Work @default.
- W3198662016 sameAs 3198662016 @default.
- W3198662016 citedByCount "0" @default.
- W3198662016 crossrefType "proceedings-article" @default.
- W3198662016 hasAuthorship W3198662016A5000410225 @default.
- W3198662016 hasAuthorship W3198662016A5013719514 @default.
- W3198662016 hasAuthorship W3198662016A5034637504 @default.
- W3198662016 hasAuthorship W3198662016A5038230299 @default.
- W3198662016 hasAuthorship W3198662016A5039256755 @default.
- W3198662016 hasAuthorship W3198662016A5039534612 @default.
- W3198662016 hasAuthorship W3198662016A5044458859 @default.
- W3198662016 hasAuthorship W3198662016A5061201309 @default.
- W3198662016 hasAuthorship W3198662016A5063266121 @default.
- W3198662016 hasAuthorship W3198662016A5064191727 @default.
- W3198662016 hasAuthorship W3198662016A5081553465 @default.
- W3198662016 hasAuthorship W3198662016A5081819845 @default.
- W3198662016 hasAuthorship W3198662016A5087588860 @default.
- W3198662016 hasAuthorship W3198662016A5089345009 @default.
- W3198662016 hasAuthorship W3198662016A5090106620 @default.
- W3198662016 hasConcept C104317684 @default.
- W3198662016 hasConcept C126322002 @default.
- W3198662016 hasConcept C134018914 @default.
- W3198662016 hasConcept C143065580 @default.
- W3198662016 hasConcept C169760540 @default.
- W3198662016 hasConcept C2778163477 @default.
- W3198662016 hasConcept C2779134260 @default.
- W3198662016 hasConcept C2780062018 @default.
- W3198662016 hasConcept C2780647506 @default.
- W3198662016 hasConcept C2781427258 @default.
- W3198662016 hasConcept C513476851 @default.
- W3198662016 hasConcept C54355233 @default.
- W3198662016 hasConcept C71924100 @default.
- W3198662016 hasConcept C86339819 @default.
- W3198662016 hasConcept C86803240 @default.
- W3198662016 hasConcept C95444343 @default.
- W3198662016 hasConceptScore W3198662016C104317684 @default.
- W3198662016 hasConceptScore W3198662016C126322002 @default.
- W3198662016 hasConceptScore W3198662016C134018914 @default.
- W3198662016 hasConceptScore W3198662016C143065580 @default.
- W3198662016 hasConceptScore W3198662016C169760540 @default.
- W3198662016 hasConceptScore W3198662016C2778163477 @default.
- W3198662016 hasConceptScore W3198662016C2779134260 @default.
- W3198662016 hasConceptScore W3198662016C2780062018 @default.
- W3198662016 hasConceptScore W3198662016C2780647506 @default.
- W3198662016 hasConceptScore W3198662016C2781427258 @default.
- W3198662016 hasConceptScore W3198662016C513476851 @default.
- W3198662016 hasConceptScore W3198662016C54355233 @default.
- W3198662016 hasConceptScore W3198662016C71924100 @default.
- W3198662016 hasConceptScore W3198662016C86339819 @default.
- W3198662016 hasConceptScore W3198662016C86803240 @default.
- W3198662016 hasConceptScore W3198662016C95444343 @default.
- W3198662016 hasLocation W31986620161 @default.
- W3198662016 hasOpenAccess W3198662016 @default.
- W3198662016 hasPrimaryLocation W31986620161 @default.
- W3198662016 hasRelatedWork W1997648025 @default.
- W3198662016 hasRelatedWork W2049314182 @default.
- W3198662016 hasRelatedWork W2050852813 @default.
- W3198662016 hasRelatedWork W2165279253 @default.
- W3198662016 hasRelatedWork W2900924817 @default.
- W3198662016 hasRelatedWork W2924015469 @default.
- W3198662016 hasRelatedWork W3004881993 @default.
- W3198662016 hasRelatedWork W3103080220 @default.
- W3198662016 hasRelatedWork W3176653513 @default.
- W3198662016 hasRelatedWork W3215349630 @default.
- W3198662016 isParatext "false" @default.
- W3198662016 isRetracted "false" @default.
- W3198662016 magId "3198662016" @default.
- W3198662016 workType "article" @default.