Leupeptin reduces impulse noise induced hearing loss

<p>Abstract</p> <p>Background</p> <p>Exposure to continuous and impulse noise can induce a hearing loss. Leupeptin is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. The objective of this study is to assess whether Leupeptin could reduce the hearing loss resulting from rifle impulse noise.</p> <p>Methods</p> <p>A polyethelene tube was implanted into middle ear cavities of eight fat sand rats (16 ears). Following determination of auditory nerve brainstem evoked response (ABR) threshold in each ear, the animals were exposed to the noise of 10 M16 rifle shots. Immediately after the exposure, saline was then applied to one (control) ear and non-toxic concentrations of leupeptin determined in the first phase of the study were applied to the other ear, for four consecutive days.</p> <p>Results</p> <p>Eight days after the exposure, the threshold shift (ABR) in the control ears was significantly greater (44 dB) than in the leupeptin ears (27 dB).</p> <p>Conclusion</p> <p>Leupeptin applied to the middle ear cavity can reduce the hearing loss resulting from exposure to impulse noise.</p

Effects of Novel Calpain Inhibitors in Transgenic Animal Model of Parkinson\u27s Disease/Dementia with Lewy Bodies

Parkinson\u27s 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

Effects of Novel Calpain Inhibitors in Transgenic Animal Model of Parkinson’s disease/dementia with Lewy bodies

Abstract Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders of the aging population characterized by the accumulation of α-synuclein (α-syn). The mechanisms triggering α-syn toxicity are not completely understood, however, c-terminus truncation of α-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 α-syn pathology in a transgenic mouse model. For this purpose, non-tg and α-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 α-syn deposition using Gabadur and a 40% reduction using Neurodur with a concomitant reduction in c-terminus α-syn and improvements in neurodegeneration. Western blot analysis showed a 77% decrease in α-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 α-syn tg mice. Taken together, this study suggests that calpain inhibition might be considered in the treatment of synucleinopathies