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P2‐084: T‐type voltage‐gated calcium channel activated by ST101 is a novel molecular target as cognitive enhancer
Author(s) -
Moriguchi Shigeki,
Fukunaga Kohji
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.788
Subject(s) - chemistry , voltage dependent calcium channel , calcium channel , hippocampal formation , pharmacology , calcium , biophysics , biology , neuroscience , organic chemistry
an increase. Accordingly, Western blotting revealed decreases in C83 and the constitutive a -secretase ADAM10, suggesting that blockade of T-type channels downregulates the non-amyloidogenic processing pathway of APP. Notably, no significant changes in tau pathology were observed. However, the cleavage of p35 to p25, which is carried out by calpains, was dramatically reduced with treatment. Further investigation revealed that calpain 1 and 2 protein levels were decreased with drug treatment. Another substrate of calpains, spectrin, was also analyzed in these samples and was found to be similarly decreased in drug-treated mice compared to controls, suggesting that T-type calcium currents contribute substantially to the regulation of calpains.Conclusions: From our results, we conclude that age-related reductions in T-type calcium channels may have the potential to push APP processing toward the amyloidogenic pathway. This could, in turn, predispose the aging brain to develop Alzheimer’s disease.