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Navigating Alzheimer’s Disease via Chronic Stress: The Role of Glucucocorticoids

Author(s):

Vivek Kumar Sharma and Thakur Gurjeet Singh*   Pages 1 - 12 ( 12 )

Abstract:


Alzheimer’s disease (AD) is a chronic, progressive, incurable neurodegenerative manifestation that not only impairs the memory and executive functions of a human being but takes away the sense of being human. The currently available drugs have provided symptomatic relief only and do not affect the underlying silent killing progression of dreaded pathology. The resultant saturation in the area of current targets (Amyloid Beta, Tau Protein, Oxidative stress, etc.) has led the scientific community to rethink the mechanistic neurodegenerative pathways and reprogram the current research directions. Although the role of stress has been known for many years the area has got the much-needed impetus recently and is being recognized as a modifiable risk factor for AD. Stress is an unavoidable human experience that the body can quickly resolve and normalize but when it becomes chronic, it may seriously perturb the physiological and psychological status of an individual. Repetitive recruitment of the neuroendocrine response to chronic stress and uncontrollable stressors are generally associated with a high risk of developing AD. Chronic stress-driven physiological dysregulation and hypercortisolemia intermingle at the neuronal level and leads to functional (hypometabolism, excitotoxicity, inflammation) and anatomical remodeling of the brain architecture (senile plaques, τ tangles, hippocampal atrophy, retraction of spines) ending with severe cognitive deterioration. The present review is an effort to collect the most relevant evidence that support chronic stress as a viable and modifiable therapeutic target for AD and to advocate glucocorticoid receptors as therapeutic interventions.

Keywords:

Stress, Glucocorticoids, HPA axis, Alzheimer’s disease, Inflammation, Amyloid β, Neurodegeneration

Affiliation:

Govt. College of Pharmacy, Rohru, District Shimla, Himachal Pradesh-171207, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab-140401



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