[Huntington chorea in Drosophila and mice: toward new therapeutic steps].
Huntington's disease is an hereditary dominant neurodegenerative disorder clinically characterised by progressive dyskinesia, cognitive decline and psychiatric disturbances. One decade after the identification of the gene whose mutation is responsible for the disease, this pathology remains incurable. However, major insights into early cellular and molecular basis of Huntington's disease have arisen from transgenic models. Transcriptional dysregulation, abnormal degradation of misfolded proteins as well as excitotoxic processes and mitochondrial dysfunction are involved in Huntington's disease. The present review discusses the recent insights gained from mouse and Drosophila models towards the understanding of pathogenesis and the development of new therapeutic tools.
Liévens
Jean-Charles
JC
Laboratoire de Génétique et Physiologie du Développement, Institut de Biologie du Développement de Marseille, Cnrs, Université de la Méditerranée, Campus de Luminy, Case 907, 13288 Marseille, France. lievens@ibdm.univ-mrs.fr
Birman
Serge
S
D000818:Animals; D030801:Animals, Genetically Modified; D003546:Cysteine Endopeptidases / Q000502:physiology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D011506:Proteins / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D009687:Nuclear Proteins; D011506:Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex