This is as close to an explanation of mechanism for bryostatin as I
could find - a synopsis of a study using mice. See below abstract.

Mary G.

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

René Etcheberrigaray *, Mathew Tan *, Ilse Dewachter , Cuno Kuipéri ,
Ingrid Van der Auwera , Stefaan Wera , Lixin Qiao *, Barry Bank *,
Thomas J. Nelson , Alan P. Kozikowski ¶, Fred Van Leuven  and Daniel
L. Alkon , ||

*NeuroLogic, Inc., Rockville, MD 20850; Experimental Genetics Group,
Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; NV reMynd,
B-3000 Leuven, Belgium; ¶Department of Medicinal Chemistry and
Pharmacognosy, College of Pharmacy, University of Illinois, Chicago,
IL 60612; and The Blanchette Rockefeller Neurosciences Institute,
Rockville, MD 20850

Communicated by Bernhard Witkop, National Institutes of Health,
Bethesda, MD, June 2, 2004 (received for review April 19, 2004)

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 memory which are also altered or
defective in AD. PKC is also involved in the processing of the amyloid
precursor protein (APP), a central element in AD pathophysiology. In
previous studies, we demonstrated that benzolactam (BL), a novel PKC
activator, reversed K+ channels defects and enhanced secretion of APP
in AD cells. In this study we present data showing that another PKC
activator, bryostatin 1, at subnanomolar concentrations dramatically
enhances the secretion of the -secretase product sAPP in fibroblasts
from AD patients. We also show that BL significantly increased the
amount of sAPP and reduced A40 in the brains of APP[V717I] transgenic
mice. In a more recently developed AD double-transgenic mouse,
bryostatin was effective in reducing both brain A40 and A42. In
addition, bryostatin ameliorated the rate of premature death and
improved behavioral outcomes. Collectively, these data corroborate PKC
and its activation as a potentially important means of ameliorating AD
pathophysiology and perhaps cognitive impairment, thus offering a
promising target for drug development. Because bryostatin 1 is devoid
of tumor-promoting activity and is undergoing numerous clinical
studies for cancer treatment in humans, it might be readily tested in
patients as a potential therapeutic agent for Alzheimer's disease.

Abbreviations: AD, Alzheimer's disease; APP, amyloid precursor
protein; sAPP, secreted form of APP; BL, benzolactam.