PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease

Abstract

There is strong evidence that protein kinase C (PKC) isozyme signaling pathways are causally involved in associative memory storage. Other observations have indicated that PKC signaling pathways regulate important molecular events in the neurodegenerative pathophysiology of Alzheimer's disease (AD), which is a progressive dementia that is characterized by loss of recent memory. This parallel involvement of PKC signaling in both memory and neurodegeneration indicates a common basis for the origins of both the symptoms and the pathology of AD. Here, we discuss this conceptual framework as a basis for an autopsy-validated peripheral biomarker--and for AD drug design targeting drugs (bryostatin and bryologs) that activate PKC isozymes--that has already demonstrated significant promise for treating both AD neurodegeneration and its symptomatic memory loss.