%0 Journal Article
%T Effects of Novel Calpain Inhibitors in Transgenic Animal Model of Parkinson¡¯s disease/dementia with Lewy bodies
%J -
%D 2018
%R https://doi.org/10.1038/s41598-018-35729-1
%X Parkinson¡¯s disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders of the aging population characterized by the accumulation of ¦Á-synuclein (¦Á-syn). The mechanisms triggering ¦Á-syn toxicity are not completely understood, however, c-terminus truncation of ¦Á-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 ¦Á-syn pathology in a transgenic mouse model. For this purpose, non-tg and ¦Á-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 ¦Á-syn deposition using Gabadur and a 40% reduction using Neurodur with a concomitant reduction in c-terminus ¦Á-syn and improvements in neurodegeneration. Western blot analysis showed a 77% decrease in ¦Á-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 ¦Á-syn tg mice. Taken together, this study suggests that calpain inhibition might be considered in the treatment of synucleinopathies
%U https://www.nature.com/articles/s41598-018-35729-1