Document Detail

High-energy compounds promote physiological processing of Alzheimer's amyloid-β precursor protein and boost cell survival in culture.
MedLine Citation:
PMID:  22906069     Owner:  NLM     Status:  Publisher    
Physiological or α-processing of amyloid-β precursor protein (APP) prevents the formation of Aβ, which is deposited in the aging brain and may contribute to Alzheimer's disease (AD). As such, drugs promoting this pathway could be useful for prevention of the disease. Along this line, we searched through a number of substances and found that a group of high-energy compounds (HECs), namely ATP, phosphocreatine and acetyl coenzyme A, potently increased APP α-processing in cultured SH-SY5Y cells, whereas their cognate counterparts, i.e. ADP, creatine or coenzyme A did not show the same effects. Other HECs such as GTP, CTP, phosphoenol pyruvate and S-adenosylmethionine also promoted APP α-processing with varying potencies and the effects were abolished by energy inhibitors rotenone or NaN(3) . The overall efficacy of the HECs in the process ranged from 3 to 4-fold, which was significantly greater than that exhibited by other physiological stimulators such as glutamate and nicotine. This suggested that the HECs were perhaps the most efficient physiological stimulators for APP α-processing in vitro. Moreover, the HECs largely offset the inefficient APP α-processing in aged human fibroblasts or in cells impaired by rotenone or H(2) O(2) . Most importantly, some HECs markedly boosted the survival rate of SH-SY5Y cells in the death process induced by energy suppression or oxidative stress. These findings suggest a new regulatory mechanism for the putative α-secretase and raise the possibility that the HECs may be useful to energize and strengthen the aging brain cells to slowdown the progression of AD. Published 2012. This article is a US Government work and is in the public domain in the USA.
Darrell R Sawmiller; Huey T Nguyen; Olga Markov; Ming Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-21
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published 2012. This article is a US Government work and is in the public domain in the USA.
Aging Research Laboratory, Bay Pines VA Healthcare System, Bay Pines, FL, 3374, USA.
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