| Autor: |
Emma Hockly, Jamie Tse, Amy L. Barker, Donna L. Moolman, Jean-Luc Beunard, Adrian P. Revington, Kim Holt, Sunny Sunshine, Hilary Moffitt, Kirupa Sathasivam, Benjamin Woodman, Erich E. Wanker, Philip A.S. Lowden, Gillian P. Bates |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 21, Iss 1, Pp 228-236 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2005.07.007 |
| Popis: |
Huntington's disease (HD) is an inherited progressive neurological disorder for which there is no effective therapy. It is caused by a CAG/polyglutamine repeat expansion that leads to abnormal protein aggregation and deposition in the brain. Several compounds have been shown to disrupt the aggregation process in vitro, including a number of benzothiazoles. To further explore the therapeutic potential of the benzothiazole aggregation inhibitors, we assessed PGL-135 and riluzole in hippocampal slice cultures derived from the R6/2 mouse, confirming their ability to inhibit aggregation with an EC50 of 40 μM in this system. Preliminary pharmacological work showed that PGL-135 was metabolically unstable, and therefore, we conducted a preclinical trial in the R6/2 mouse with riluzole. At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 μM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect