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

摘要

Cytosolic brain-type creatine kinase (BB-CK), which is coexpressedwith ubiquitous mitochondrial uMtCK, is significantly inactivatedby oxidation in Alzheimer's disease (AD) patients. Since CK hasbeen shown to play a fundamental role in cellular energetics ofthe brain, any disturbance of this enzyme may exasperate the ADdisease process. Mutations in amyloid precursor protein (APP) areassociated with early onset AD and result in abnormal processingof APP, and accumulation of Aβ peptide, the mainconstituent of amyloid plaques in AD brain. Recent data on adirect interaction between APP and the precursor of uMtCK supportan emerging relationship between AD, cellular energy levels, andmitochondrial function. In addition, recently discovered creatine(Cr) deposits in the brain of transgenic AD mice, as well as inthe hippocampus from AD patients, indicate a direct link betweenperturbed energy state, Cr metabolism, and AD. Here, we review theroles of Cr and Cr-related enzymes and consider the potentialvalue of supplementation with Cr, a potent neuroprotectivesubstance. As a hypothesis, we consider whether Cr, if given at anearly time point of the disease, may prevent or delay the courseof AD-related neurodegeneration.