Forkhead transcription factors: new considerations for alzheimer’s disease and dementia

Jul 9, 2016Journal of translational science

New insights on forkhead proteins in Alzheimer's disease and dementia

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Abstract

Almost ten percent of the population over the age of 65 suffers from Alzheimer's disease (AD).

Life expectancy is rising globally, correlating with an increase in chronic neurodegenerative disorders like AD.
AD currently has no definitive therapy to prevent cognitive loss.
FoxO transcription factors are found in key brain areas associated with memory, such as the hippocampus and amygdala.
FoxOs are involved in the survival of various nerve cell types and regulate processes like cell death and recycling.
These factors interact with several cellular pathways that may influence cell fate and cognitive functions.

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Life expectancy of individuals in both developed and undeveloped nations continues to rise at an unprecedented rate. Coupled to this increase in longevity for individuals is the rise in the incidence of chronic neurodegenerative disorders that includes Alzheimer's disease (AD). Currently, almost ten percent of the population over the age of 65 suffers from AD, a disorder that is presently without definitive therapy to prevent the onset or progression of cognitive loss. Yet, it is estimated that AD will continue to significantly increase throughout the world to impact millions of individuals and foster the escalation of healthcare costs. One potential target for the development of novel strategies against AD and other cognitive disorders involves the mammalian forkhead transcription factors of the O class (FoxOs). FoxOs are present in "cognitive centers" of the brain to include the hippocampus, the amygdala, and the nucleus accumbens and may be required for memory formation and consolidation. FoxOs play a critical role in determining survival of multiple cell types in the nervous system, drive pathways of apoptosis and autophagy, and control stem cell proliferation and differentiation. FoxOs also interface with multiple cellular pathways that include growth factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), and silent mating type information regulation 2 homolog 1 () (SIRT1) that ultimately may control FoxOs and determine the fate and function of cells in the nervous system that control memory and cognition. Future work that can further elucidate the complex relationship FoxOs hold over cell fate and cognitive function could yield exciting prospects for the treatment of a number of neurodegenerative disorders including AD. Saccharomyces cerevisiae

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Forkhead transcription factors: new considerations for alzheimer’s disease and dementia

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