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- W2266528079 abstract "Glucose hypo-metabolism is an early feature in Alzheimer's disease (AD), preceding the onset of the clinical symptoms of dementia and the appearance of amyloidbeta (Aβ) peptide, a proteolytic product of amyloid precursor protein (APP). Studies showed that this metabolic deficit is associated with altered expression and activity of enzymes involved in mitochondrial energy production. Mitochondrial dysfunction can lead to ATP depletion and trigger apoptosis. Inhibition of energy metabolism can also alter APP processing. Hence, buffering intracellular energy levels could exert neuroprotective effects. One such buffering system is creatine kinase and its substrate creatine. However, it is unclear if energy buffering can modulate aberrant APP processing. In human brain, APP695 is the predominant APP isoforms and APP751 and APP770 are two other major APP transcripts. APP751 and APP770 isoforms contain a Kunitz protease inhibitory (KPI) motif that APP695 lacks, and APP770 possesses an additional OX2 domain that is absent in both APP695 and APP751. In AD-afflicted human brain tissues, APP751 and APP770 expression were elevated. In this study using an immortalized APP-null neuronal cell line expressing APP695, APP751 and APP77, we observed creatine is able to reduce the production of amyloidogenic derivatives and lessen the impairment of mitochondrial function in cells expressing the KPI-containing APP isoforms. This neuroprotective effect is due in part to the activation of the insulin signalling pathway. Taken together, we speculate that creatine may have an important role in preventing energy dysfunction and possibly modulating the neurodegenerative cascade in AD." @default.
- W2266528079 created "2016-06-24" @default.
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- W2266528079 date "2008-03-01" @default.
- W2266528079 modified "2023-09-25" @default.
- W2266528079 title "Effect of creatine on the processing of amyloid precursor protein isoforms and mitochondrial function." @default.
- W2266528079 doi "https://doi.org/10.1096/fasebj.22.1_supplement.823.11" @default.
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