title: [On what I learned from researches on Huntington's disease].
abstract: In the Presidential Lecture, I looked back my 28 years' history of researches on Huntington's disease (HD). In the first 3-4 years, I worked predominantly in the field of the neuro-anatomy, elucidating the fine distribution of the inhibitory neurotransmitter, GABA, in the human substantia nigra, elucidating the existence of a hitherto unknown subthalamo-nigral pathway in rat, and demonstrating the presence of the excitatory substance P-ergic striatonigral pathway in rat. In the middle 16-17 years, I preferentially worked in the field of neurochemical pharmacology, suggesting a mechanism of chorea in HD to be a result of hyperactivity of remaining presynaptic dopaminergic system in the striatum by making a 'choreic' model in monkey using excitotoxic kainic acid and levodopa. In the last 7-8 years, we began to be involved in the analysis of huntington gene of patients and protein chemistry of intranuclear inclusion bodies appeared in culture cells, based on the concept that HD is a CAG repeat disease. We found that the forming process of inclusion bodies was unexpectedly rapid. In addition, we found that inclusion bodies not only contain huntington itself but also contain histones, splicosomes, and ubiquitin. The recruitment of those biologically important proteins into the inclusion bodies could give neurons serious damages for living normally, even if not directly to a catastrophe, a neuronal death.
authors.affiliation: Department of Neurology, School of Medicine, Tokyo University.
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000818:Animals; D003342:Corpus Striatum; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000473:pathology; D002479:Inclusion Bodies / Q000737:chemistry; D018377:Neurotransmitter Agents; D051381:Rats; D013373:Substance P; D013378:Substantia Nigra; D019680:Trinucleotide Repeat Expansion; D005680:gamma-Aminobutyric Acid
chemical_list: D018377:Neurotransmitter Agents; D013373:Substance P; D005680:gamma-Aminobutyric Acid