Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice

• DOI: 10.1073/pnas.0403921101
• Publication Date: 2004-07-20T00:17:21Z
• Authors: René Etcheberrigaray; Mathew Tan; Ilse Dewachter; Cuno Kuipéri; Ingrid Van der Au...; Stefaan Wera; Lixin Qiao; Barry Bank; Thomas J. Nelson; Alan P. Kozikowski; Fred Van Leuven; Daniel L. Alkon
• Keywords: Bryostatin 1

Alzheimer's disease (AD) characteristically presents with early memory loss. Regulation of K + channels, calcium homeostasis, and protein kinase C (PKC) activation are molecular events that have been implicated during associative which also altered or defective in AD. PKC is involved the processing amyloid precursor (APP), a central element AD pathophysiology. In previous studies, we demonstrated benzolactam (BL), novel activator, reversed channels defects enhanced secretion APPα cells. this study present data showing another bryostatin 1, at subnanomolar concentrations dramatically enhances α-secretase product sAPPα fibroblasts from patients. We show BL significantly increased amount reduced Aβ40 brains APP[V717I] transgenic mice. more recently developed double-transgenic mouse, was effective reducing both brain Aβ42. addition, ameliorated rate premature death improved behavioral outcomes. Collectively, these corroborate its as potentially important means ameliorating pathophysiology perhaps cognitive impairment, thus offering promising target for drug development. Because 1 devoid tumor-promoting activity undergoing numerous clinical studies cancer treatment humans, it might be readily tested patients potential therapeutic agent disease.