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 Aβ 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.
