pPKCα-mediated effect on in vitro Aβ production in response to gamma secretase inhibitor LY411575 in rat CTXTNA2 astrocytes

Abstract

Alzheimers Disease implies memory and cognitive impairment due to beta amyloid accumulation, presence of reactive microglia and astrocytes, loss of synapses, neural network dysfunctions and modifications of neuronal signalling. A key role in such events is played by astrocytes, which actively secrete high levels of beta amyloid protein originating from sequential cleavage of APP by alpha, beta and gamma secretases. Since inhibition of such process could represent an important strategy against the occurrence of Alzheimers Disease, in this paper the role played by pPKC alpha in the in vitro beta amyloid production in response to gamma secretase inhibitor in rat cortical astrocytes is reported. pPKC alpha increased expression seems to be related to decreased beta amyloid production in parallel to increased astrocytes viability and decreased iNOS expression in the presence of 10 microM LY411575. Thus gamma secretase inhibitor, activating pPKC alpha intracellular pathway could be suggested to prevent or reduce downstream toxic events, representing a useful strategy to counteract Alzheimers disease.