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000259914 1001_ $$00000-0002-4182-0764$$aVoelkl, Kerstin$$b0
000259914 245__ $$aNeuroprotective effects of hepatoma-derived growth factor in models of Huntington's disease.
000259914 260__ $$aHeidelberg$$bEMBO Press$$c2023
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000259914 520__ $$aHuntington's disease (HD) is a movement disorder caused by a mutation in the Huntingtin gene that leads to severe neurodegeneration. Molecular mechanisms of HD are not sufficiently understood, and no cure is currently available. Here, we demonstrate neuroprotective effects of hepatoma-derived growth factor (HDGF) in cellular and mouse HD models. We show that HD-vulnerable neurons in the striatum and cortex express lower levels of HDGF than resistant ones. Moreover, lack of endogenous HDGF exacerbated motor impairments and reduced the life span of R6/2 Huntington's disease mice. AAV-mediated delivery of HDGF into the brain reduced mutant Huntingtin inclusion load, but had no significant effect on motor behavior or life span. Interestingly, both nuclear and cytoplasmic versions of HDGF were efficient in rescuing mutant Huntingtin toxicity in cellular HD models. Moreover, extracellular application of recombinant HDGF improved viability of mutant Huntingtin-expressing primary neurons and reduced mutant Huntingtin aggregation in neural progenitor cells differentiated from human patient-derived induced pluripotent stem cells. Our findings provide new insights into the pathomechanisms of HD and demonstrate neuroprotective potential of HDGF in neurodegeneration.
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000259914 650_2 $$2MeSH$$aMice
000259914 650_2 $$2MeSH$$aHumans
000259914 650_2 $$2MeSH$$aAnimals
000259914 650_2 $$2MeSH$$aHuntington Disease: genetics
000259914 650_2 $$2MeSH$$aHuntington Disease: drug therapy
000259914 650_2 $$2MeSH$$aHuntington Disease: metabolism
000259914 650_2 $$2MeSH$$aNeuroprotective Agents: pharmacology
000259914 650_2 $$2MeSH$$aNeuroprotective Agents: metabolism
000259914 650_2 $$2MeSH$$aNeuroprotective Agents: therapeutic use
000259914 650_2 $$2MeSH$$aNeurons: metabolism
000259914 650_2 $$2MeSH$$aIntercellular Signaling Peptides and Proteins: metabolism
000259914 650_7 $$2NLM Chemicals$$aNeuroprotective Agents
000259914 650_7 $$2NLM Chemicals$$ahepatoma-derived growth factor
000259914 650_7 $$2NLM Chemicals$$aIntercellular Signaling Peptides and Proteins
000259914 7001_ $$aGutiérrez-Ángel, Sara$$b1
000259914 7001_ $$00000-0002-6413-2550$$aKeeling, Sophie$$b2
000259914 7001_ $$aKoyuncu, Seda$$b3
000259914 7001_ $$ada Silva Padilha, Miguel$$b4
000259914 7001_ $$aFeigenbutz, Dennis$$b5
000259914 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b6$$udzne
000259914 7001_ $$00000-0002-0801-0743$$aVilchez, David$$b7
000259914 7001_ $$00000-0002-3109-0163$$aKlein, Rüdiger$$b8
000259914 7001_ $$00000-0003-1052-8485$$aDudanova, Irina$$b9
000259914 773__ $$0PERI:(DE-600)2948687-7$$a10.26508/lsa.202302018$$gVol. 6, no. 11, p. e202302018 -$$n11$$pe202302018$$tLife science alliance$$v6$$x2575-1077$$y2023
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