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The Creatine Kinase/Creatine Connection to Alzheimer's Disease: CK Inactivation, APP-CK Complexes and Focal Creatine Deposits

Abstract : Cytosolic brain-type creatine kinase (BB-CK), which is coexpressed with ubiquitous mitochondrial uMtCK, is significantly inactivated by oxidation, in Alzheimer's disease (AD) patients. Since CK has been shown to play a fundamental role in cellular energetics of the brain, any disturbance of this enzyme may exasperate the AD disease process. Mutations in amyloid precursor protein (APP) are associated with early onset AD and result in abnormal processing of APP, and accumulation of A beta peptide, the main constituent of amyloid plaques in AD brain. Recent data on a direct interaction between APP and the precursor of uMtCK support an emerging relationship between AD, cellular energy levels and mitochondrial function. In addition, recently discovered creatine (Cr) deposits in the brain of transgenic AD mice, as well as in the hippocampus from AD patients, indicate a direct link between perturbed energy state, Cr metabolism and AD. Here, we review the roles of Cr and Cr-related enzymes and consider the potential value of supplementation with Cr, a potent neuroprotective substance. As a hypothesis, we consider whether Cr, if given at an early time point of the disease, may prevent or delay the course of AD-related neurodegeneration.
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https://hal.univ-grenoble-alpes.fr/hal-01987746
Contributeur : Sarah Hamant <>
Soumis le : lundi 21 janvier 2019 - 12:01:37
Dernière modification le : mercredi 15 juillet 2020 - 09:10:04

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Tanja Bürklen, Uwe Schlattner, Ramin Homayouni, Kathleen Gough, Margaret Rak, et al.. The Creatine Kinase/Creatine Connection to Alzheimer's Disease: CK Inactivation, APP-CK Complexes and Focal Creatine Deposits. Journal of Biomedicine and Biotechnology, Hindawi Publishing Corporation, 2006, 2006, pp.1-11. ⟨10.1155/JBB/2006/35936⟩. ⟨hal-01987746⟩

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