title: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease.
abstract: Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide seem to play a role in Huntington disease, we evaluated the therapeutic efficacy of minocycline in the R6/2 mouse model of Huntington disease. We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model.
authors.affiliation: Neuroapoptosis Laboratory, Neurosurgical Service, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: V O
authors.initials: VO
authors.lastname: Ona
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: R J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: K B
authors.initials: KB
authors.lastname: Fink
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Bian
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: L A
authors.initials: LA
authors.lastname: Farrell
authors.forename: S M
authors.initials: SM
authors.lastname: Hersch
authors.forename: W
authors.initials: W
authors.lastname: Hobbs
authors.forename: J P
authors.initials: JP
authors.lastname: Vonsattel
authors.forename: J H
authors.initials: JH
authors.lastname: Cha
authors.forename: R M
authors.initials: RM
authors.lastname: Friedlander
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D020170:Caspase 1 / Q000096:biosynthesis*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D005069:Evaluation Studies as Topic; D005786:Gene Expression Regulation; D006816:Huntington Disease / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008822:Mice, Transgenic; D008911:Minocycline / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D008911:Minocycline