Role of the SNK-SPAR Pathway in the Development of Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the presence of senile plaques and neurofibrillary tangles in the brain. The beta-amyloid peptide (A beta) is the primary constituent of the senile plaques, and has been proposed to be a key contributor to the neurodegeneration observed in AD. The molecular mechanisms underlying dendritic spine damage that is induced by A beta toxicity in AD patients remain largely unknown. It has been suggested previously that the SNK-SPAR signaling pathway is involved in activity-dependent remodeling of synapses. The relationship between the SNK-SPAR pathway and A beta-induced excitotoxicity, however, is poorly understood. The present study investigated the effects of bilateral intrahippocampal injection of A beta peptide 1-40 (A beta(1-40)) on learning and memory in the rat, and explored the mechanisms underlying the effects of this injection. We reported that bilateral injection of A beta(1-40) in rats resulted in impaired performance in the step-down passive avoidance and Morris water maze tasks. Then we examined mRNA and protein expression levels in the different brain regions one week after injection with A beta(1-40) and found that the SNK-SPAR signaling pathway was possibly involved in dendritic spine damage in the different brain regions of A beta-treated rats. These results demonstrate that the SNK-SPAR pathway may possibly play a crucial role in A beta-induced excitotoxic damage in the central nervous system by regulating synaptic stability. (C) 2010 IUBMB IUBMB Life, 62(3): 214-221, 2010