Multi-kinase inhibitors either by themselves or in combination with strategies currently being used such as immunotherapy or secretase inhibitors for AD and knockdown for HD could represent a more effective therapeutic approach for these fatal neurodegenerative diseases.Īlzheimer’s disease (AD) is a mostly sporadic brain disorder characterized by progressive cognitive decline resulting from neurodegeneration that starts in the entorhinal cortex and progresses to the hippocampus and large portions of the cerebral cortex. The potential of targeting GSK3, p38 MAPK and CDKS as effective therapeutics is also discussed as is a brief discussion on the utilization of recently developed drugs that simultaneously target two or all three of these groups of kinases. After a brief summary of the molecular and cell biology of AD and HD this review covers what is known about the role of these three groups of kinases in the brain and in the pathogenesis of the two neurodegenerative disorders. Prominent among these kinases are glycogen synthase kinase (GSK3), p38 mitogen-activated protein kinase (MAPK) and some of the cyclin-dependent kinases (CDKs).

Research conducted over the past three decades by a large number of laboratories has demonstrated that abnormal actions of common kinases play a key role in the pathogenesis of both AD and HD as well as several other neurodegenerative diseases.

Although there have been numerous clinical trials for these diseases, they have been unsuccessful. Alzheimer’s disease (AD) is a mostly sporadic brain disorder characterized by cognitive decline resulting from selective neurodegeneration in the hippocampus and cerebral cortex whereas Huntington’s disease (HD) is a monogenic inherited disorder characterized by motor abnormalities and psychiatric disturbances resulting from selective neurodegeneration in the striatum.

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