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 (Abeta) 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 Abeta 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 Abeta-induced excitotoxicity, however, is poorly understood. The present study investigated the effects of bilateral intrahippocampal injection of Abeta peptide 1-40 (Abeta(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 Abeta(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 Abeta(1-40) and found that the SNK-SPAR signaling pathway was possibly involved in dendritic spine damage in the different brain regions of Abeta-treated rats. These results demonstrate that the SNK-SPAR pathway may possibly play a crucial role in Abeta-induced excitotoxic damage in the central nervous system by regulating synaptic stability.
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Dalian Medical University, Liaoning Province, China.
Xiaoyang
X
Gong
Xiaoguang
X
Lu
Libin
L
Zhan
Hua
H
Sui
Xin
X
Qi
Zhenghong
Z
Ji
Xinping
X
Niu
Li
L
Liu
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects; D010446:Peptide Fragments; D011494:Protein Kinases / Q000096:biosynthesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D020690:GTPase-Activating Proteins; D010446:Peptide Fragments; C479629:Sipa1l1 protein, rat; C078592:amyloid beta-protein (1-40); D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase