| Title | Therapeutic effects of cystamine in a murine model of Huntington's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2002 |
| Authors | Dedeoglu A, Kubilus JK, Jeitner TM, Matson SA, Bogdanov M, Kowall NW, Matson WR, Cooper AJL, Ratan RR, M Beal F, Hersch SM, Ferrante RJ |
| Journal | J Neurosci |
| Volume | 22 |
| Issue | 20 |
| Pagination | 8942-50 |
| Date Published | 2002 Oct 15 |
| ISSN | 1529-2401 |
| Keywords | Administration, Oral, Aged, Animals, Behavior, Animal, Biomarkers, Body Weight, Caudate Nucleus, Cystamine, Dipeptides, Disease Models, Animal, Enzyme Activation, Female, GTP-Binding Proteins, Humans, Huntington Disease, Injections, Intraperitoneal, Male, Mice, Mice, Transgenic, Middle Aged, Motor Activity, Neocortex, Neurons, Neuroprotective Agents, Protein Glutamine gamma Glutamyltransferase 2, Survival Rate, Transglutaminases, Treatment Outcome |
| Abstract | The precise cause of neuronal death in Huntington's disease (HD) is unknown. Proteolytic products of the huntingtin protein can contribute to toxic cellular aggregates that may be formed in part by tissue transglutaminase (Tgase). Tgase activity is increased in HD brain. Treatment in R6/2 transgenic HD mice, using the transglutaminase inhibitor cystamine, significantly extended survival, improved body weight and motor performance, and delayed the neuropathological sequela. Tgase activity and N(Sigma)-(gamma-L-glutamyl)-L-lysine (GGEL) levels were significantly altered in HD mice. Free GGEL, a specific biochemical marker of Tgase activity, was markedly elevated in the neocortex and caudate nucleus in HD patients. Both Tgase and GGEL immunoreactivities colocalized to huntingtin aggregates. Cystamine treatment normalized transglutaminase and GGEL levels in R6/2 mice. These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients. |
| Alternate Journal | J Neurosci |
| PubMed ID | 12388601 |
| PubMed Central ID | PMC6757687 |
| Grant List | AG 14930 / AG / NIA NIH HHS / United States NS 38180 / NS / NINDS NIH HHS / United States AG13846 / AG / NIA NIH HHS / United States P01 AG012992 / AG / NIA NIH HHS / United States R01 AT000613 / AT / NCCIH NIH HHS / United States NS37102 / NS / NINDS NIH HHS / United States AG12992 / AG / NIA NIH HHS / United States R01 NS039258 / NS / NINDS NIH HHS / United States P01 AG014930 / AG / NIA NIH HHS / United States NS35255 / NS / NINDS NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States U01 AT000613 / AT / NCCIH NIH HHS / United States AT00613 / AT / NCCIH NIH HHS / United States NS 39258 / NS / NINDS NIH HHS / United States |
Related Institute:
Molecular Imaging Innovations Institute (MI3)