HDAC4 regulates neuronal survival in normal and diseased retinas.
Bo Chen,Constance L. Cepko +1 more
TLDR
Evidence is provided that HDAC4 plays an important role in promoting the survival of retinal neurons and relied at least partly on the activity of hypoxia-inducible factor 1α (HIF1α) in the cytoplasm.Abstract:
Histone deacetylase 4 (HDAC4) shuttles between the nucleus and cytoplasm and serves as a nuclear co-repressor that regulates bone and muscle development. We report that HDAC4 regulates the survival of retinal neurons in the mouse in normal and pathological conditions. Reduction in HDAC4 expression during normal retinal development led to apoptosis of rod photoreceptors and bipolar (BP) interneurons, whereas overexpression reduced naturally occurring cell death of the BP cells. HDAC4 overexpression in a mouse model of retinal degeneration prolonged photoreceptor survival. The survival effect was due to the activity of HDAC4 in the cytoplasm and relied at least partly on the activity of hypoxia-inducible factor 1α (HIF1α). These data provide evidence that HDAC4 plays an important role in promoting the survival of retinal neurons.read more
Citations
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Histone deacetylase inhibitors: Potential in cancer therapy.
Paul A. Marks,W.-S. Xu +1 more
TL;DR: The role of histone deacetylases (HDAC) and the potential of these enzymes as therapeutic targets for cancer, neurodegenerative diseases and a number of other disorders is an area of rapidly expanding investigation.
Journal ArticleDOI
Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa
Volker Busskamp,Jens Duebel,D. Balya,Mathias Fradot,Mathias Fradot,Mathias Fradot,Tim J. Viney,Sandra Siegert,Anna C. Groner,Erik Cabuy,Valérie Forster,Valérie Forster,Valérie Forster,Mathias W. Seeliger,Martin Biel,Peter Humphries,Michel Paques,Saddek Mohand-Said,Didier Trono,Karl Deisseroth,José-Alain Sahel,Serge Picaud,Botond Roska +22 more
TL;DR: It is shown that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa.
Journal ArticleDOI
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait
TL;DR: The genetic and mechanistic causes of retinal degeneration due to PR cell death — which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration — are being successfully dissected.
Journal ArticleDOI
Targeting the correct HDAC(s) to treat cognitive disorders
Andre Fischer,Farahnaz Sananbenesi,Alison Mungenast,Alison Mungenast,Alison Mungenast,Li-Huei Tsai,Li-Huei Tsai,Li-Huei Tsai +7 more
TL;DR: The specific roles of each HDAC protein and the possible function of distinct histone modifications are discussed, in the hope that this knowledge will aid in the development of diagnostic tools and in designing more potent and specific treatment for neurological disorders targeting selective HDAC proteins.
Journal ArticleDOI
A DNAJB Chaperone Subfamily with HDAC-Dependent Activities Suppresses Toxic Protein Aggregation
Jurre Hageman,Maria A. Rujano,Maria A.W.H. van Waarde,Vaishali Kakkar,Ron P. Dirks,Natalia Govorukhina,Henderika M.J. Oosterveld-Hut,Nicolette H. Lubsen,Harm H. Kampinga +8 more
TL;DR: Combined data provide a functional link between HDACs and DNAJs in suppressing cytotoxic protein aggregation and DNAJB8 is (de)acetylated at two conserved C-terminal lysines that are not involved in substrate binding, but do play a role in suppressing protein aggregation.
References
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