Human Nck-associated protein 1 and its binding protein affect the metabolism of beta-amyloid precursor protein with Swedish mutation.
Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system, and beta-amyloid precursor protein (betaAPP) plays a pivotal role in AD pathology. We previously reported that the suppression of human Nck-associated protein 1 (Nap1) whose expression was down-regulated in sporadic AD led to apoptosis in human neuroblastoma cells, and also its binding protein, hNap1BP was identified. Here, we examined whether these molecules were involved in the regulation of betaAPP metabolism. Human Nap1 and hNap1BP were found not to effect the amount of intracellular betaAPP but induced sAPPalpha secretion. Interestingly, they didn't reduce but slightly increased the extracellular level of Abeta. Furthermore, neither human Nap1 nor hNap1BP influenced the ratio of Abeta42/43 to total Abeta. Taken together, human Nap1 and hNap1BP may play a role in regulation of beta-secretase activity in the processing of betaAPP.
Yamamoto
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A
Independent Research Group Neurodegeneration, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany.
Behl
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C
D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D009154:Mutation
D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C484362:NCKAP1 protein, human