| First Author | Hassen GW | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 18083 |
| PubMed ID | 30591714 | Mgi Jnum | J:268147 |
| Mgi Id | MGI:6271073 | Doi | 10.1038/s41598-018-35729-1 |
| Citation | Hassen GW, et al. (2018) Effects of Novel Calpain Inhibitors in Transgenic Animal Model of Parkinson's disease/dementia with Lewy bodies. Sci Rep 8(1):18083 |
| abstractText | Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders of the aging population characterized by the accumulation of alpha-synuclein (alpha-syn). The mechanisms triggering alpha-syn toxicity are not completely understood, however, c-terminus truncation of alpha-syn by proteases such as calpain may have a role. Therefore, inhibition of calpain may be of value. The main objective of this study was to evaluate the effects of systemically administered novel low molecular weight calpain inhibitors on alpha-syn pathology in a transgenic mouse model. For this purpose, non-tg and alpha-syn tg mice received the calpain inhibitors - Gabadur, Neurodur or a vehicle, twice a day for 30 days. Immunocytochemical analysis showed a 60% reduction in alpha-syn deposition using Gabadur and a 40% reduction using Neurodur with a concomitant reduction in c-terminus alpha-syn and improvements in neurodegeneration. Western blot analysis showed a 77% decrease in alpha-spectrin breakdown products (SBDPs) SBDPs with Gabadur and 63% reduction using Neurodur. There was a 65% reduction in the active calpain form with Gabadur and a 45% reduction with Neurodur. Moreover, treatment with calpain inhibitors improved activity performance of the alpha-syn tg mice. Taken together, this study suggests that calpain inhibition might be considered in the treatment of synucleinopathies. |
