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Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

Author(s):

Sunpreet Kaur, Puneet Kumar and Shamsher Singh*   Pages 1 - 20 ( 20 )

Abstract:


Background: Alzheimer’s disease is a most common neurodegenerative disorder affecting the elderly population and a leading challenge for the scientific research community. The wide pathological aspects of AD made it multifactorial disorder and even after a long time still there is no known cause and cure.

Methods: Several hypotheses regarding etiogenesis of AD targets mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. These proteins disrupt neuronal signalling, enhance oxidative stress and altered activity of various cellular enzymes which leads to neurodegeneration in cerebral cortex, neocortex and hippocampus. Some metals like copper, aluminium are involved in APP trafficking and promote amyloid beta aggregation. Similarly, disturbed ubiquitin proteosomal system and autophagy mechanism via down regulation of mTOR reduces amyloid beta clearance and exert toxic insult in brain.

Result and conclusion: The current report will shed a light upon the role of oxidative stress in disrupt amyloid homeostasis leads to amyloid beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies to the use of anticholinestrase, antioxidant, MMP inhibitors and metal chelator but they are not specific measures. Therefore, in this review we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

Keywords:

Oxidative stress, Alzheimer’s disease, Amyloid-beta proteins, Ubiquitin Proteasomal System, Insulin-degrading enzymes

Affiliation:

Neuroscience Division, Department of Pharmacology, I.S.F. College of Pharmacy, Moga; Punjab, Department of Pharmaceutical Sciences, Maharaja Ranjit Singh Punjab Technical University, Bathinda; Punjab, Neuroscience Division, Department of Pharmacology, I.S.F. College of Pharmacy, Moga; Punjab



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