Changes in protein kinases in brain aging and Alzheimer's disease. Implications for drug therapy.
There is ample evidence for the involvement of aberrant protein phosphorylation reactions in aging and age-associated neurological disorders. Alzheimer's disease (AD) in particular. The exact nature of this involvement, however, is not yet elucidated. In the brain tissue of AD patients, there are numerous examples of altered protein phosphorylation pathways. Individual protein kinases and phosphorylation by these kinases in AD brain tissues have been found to be altered. Protein kinases studied include protein kinase C (PKC), protein tyrosine kinase (PTK), casein kinase II (CKII), Ca++/calmodulin-dependent kinase II and mitogen-activated protein (MAP) kinases, all of which are thought to be necessary for cell survival. Interestingly, different protein kinases are involved in different aspects of AD pathology. It is postulated that the perturbation of amyloid beta/A4-protein precursor (APP) metabolism triggers abnormal protein phosphorylation reactions responsible for dysfunction and eventual death of neurons in the brain. The association of APP mutation with certain familial types of AD strongly suggests that there might be a link between aberrant APP metabolism, protein phosphorylation cascades and the eventual expression of AD pathology (plaques and tangles) and neurodegeneration. In summary, recent studies emphasise the prime importance of protein phosphorylation in aging and AD. This raises the possibility that future pharmacological interventions might be devised to interfere with this kinase cascade for the prevention or treatment of age-associated neurological disorders.
Jin
L W
LW
Department of Neurosciences, University of California, San Diego, USA.
Saitoh
T
T
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology
D011494:Protein Kinases