Alternative Strategy for Alzheimer’s Disease: Stress Response Triggers

Abstract

Stress resistance capacity is a hallmark of longevity protection and survival throughout the plant and animal kingdoms. Latent pathway activation of protective cascades, triggered by environmental challenges to tolerate heat, oxygen deprivation, reactive oxygen species (ROS), diet restriction, and exercise provides tolerance to these stresses. Age-related changes and disease vulnerability mark an increase in damage, like damage induced by environmental challenges. An alternative approach to immunotherapy intervention in Alzheimer's Disease is the use of mimetics of stress to upregulate endogenous protective cascades to repair age damage, shift the balance of apoptosis to regeneration to promote delay of onset, and even progression of Alzheimer's disease memory dysfunction. Mimetics of environmental stress, hormetic agents, and triggers, endogenous or engineered, can “trick” activation of expression patterns of repair and rejuvenation. Examples of known candidate triggers of heat response, endogenous antioxidants, DNA repair, exercise, hibernation, and telomeres are available for AD intervention trials. Telomeres and telomerase emerge as major regulators in crossroads of senescence, cancer, and rejuvenation responsive to mimetics of telomeres. Lessons emerge from transgenic rodent models, the long-lived mole rat, clinical studies, and conserved innate pathways of stress resistance. Cross-reaction of benefits of different triggers promises intervention into seemingly otherwise unrelated diseases.