Bibliographic
Previous studies showed that Bryostatin-1, a potent PKC modulator and alpha-secretase activator, can improve cognition in animal models of Alzheimer’s disease (AD). In this report the authors compared the efficacy of acute intraperitoneal and oral Bryostatin-1 in reversing cognitive deficits in learning and spatial memory in the APPswe, PSEN1dE9 (APP/PS1) mouse model of AD. Results indicate that acute i.p. Bryostatin-1 administration did not improve latency to escape but oral Bryostatin-1 significantly improved memory (measured by a reduction in latency to escape). This benefit of oral Bryostatin-1 administration was dose dependent and most apparent during the first 3 days of testing. In addition, oral Bryostatin-1 treatment was found to reduce amyloid plaque formation in APP/PS1 transgenic mice in a dose-dependent manner. These findings show that: 1) Bryostatin-1 is orally active in models of learning and memory, 2) this effect can be produced in less than 2 weeks and 3) this effect is not seen with i.p. administration.This study suggests that the development of orally available alpha-secretase modulators like Bryostatin-1 may represent an important part of the pharmacologic armamentarium against neurodegenerative diseases like Alzheimer’s disease and amyloid related neuropathies e.g. Down’s syndrome and cerebral amyloid angiopathies.