NYMC Faculty Publications

First Page

18083

Document Type

Article

Publication Date

12-1-2018

Department

Emergency Medicine

Abstract

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.

Comments

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Publisher's Statement

Originally published in Scientific Reports, 8 [Article 18083]. The original material can be found here.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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