Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease
| Autor: | Wayne R. Matson, Christina K. Edgerly, Daniel J. Amante, Clemens R. Scherzer, Olivia L. Bordiuk, Steven M. Hersch, Karen M. Smith, Robert J. Ferrante, Samantha Matson, Jennifer P. Moody, Jinho Kim, H. Diana Rosas |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Central Nervous System
Male Buffy coat Disease Gastroenterology Mice 0302 clinical medicine 0303 health sciences biology Huntington's disease Energetic defects Middle Aged 3. Good health Huntington Disease medicine.anatomical_structure Biomarker (medicine) Molecular Medicine Female medicine.medical_specialty Central nervous system Down-Regulation Mice Transgenic Article 03 medical and health sciences Internal medicine Creatine Kinase BB Form medicine Animals Humans Creatine kinase Molecular Biology Aged 030304 developmental biology business.industry Case-control study Biomarker medicine.disease Mice Inbred C57BL Blood buffy coat Clinical research Endocrinology Case-Control Studies Postmortem Changes Mice Inbred CBA biology.protein business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1802(7-8):673-681 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2010.05.001 |
| Popis: | A major goal of current clinical research in Huntington's disease (HD) has been to identify preclinical and manifest disease biomarkers, as these may improve both diagnosis and the power for therapeutic trials. Although the underlying biochemical alterations and the mechanisms of neuronal degeneration remain unknown, energy metabolism defects in HD have been chronicled for many years. We report that the brain isoenzyme of creatine kinase (CK-BB), an enzyme important in buffering energy stores, was significantly reduced in presymptomatic and manifest disease in brain and blood buffy coat specimens in HD mice and HD patients. Brain CK-BB levels were significantly reduced in R6/2 mice by approximately 18% to approximately 68% from 21 to 91 days of age, while blood CK-BB levels were decreased by approximately 14% to approximately 44% during the same disease duration. Similar findings in CK-BB levels were observed in the 140 CAG mice from 4 to 12 months of age, but not at the earliest time point, 2 months of age. Consistent with the HD mice, there was a grade-dependent loss of brain CK-BB that worsened with disease severity in HD patients from approximately 28% to approximately 63%, as compared to non-diseased control patients. In addition, CK-BB blood buffy coat levels were significantly reduced in both premanifest and symptomatic HD patients by approximately 23% and approximately 39%, respectively. The correlation of CK-BB as a disease biomarker in both CNS and peripheral tissues from HD mice and HD patients may provide a powerful means to assess disease progression and to predict the potential magnitude of therapeutic benefit in this disorder. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect