Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer's Disease.
Bidemi Emmanuel EkundayoTajudeen Olabisi ObafemiOlusola Bolaji AdewaleBlessing Ariyo ObafemiBabatunji Emmanuel OyinloyeStella Kemilola EkundayoPublished in: Cell biochemistry and biophysics (2024)
Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aβ) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aβ deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS). ER Stress describes the accumulation of misfolded and unfolded proteins as a result of physiological and pathological stimuli including high protein demand, toxins, inflammatory cytokines, and mutant protein expression that disturbs ER homeostasis. When compared to age-matched controls, postmortem brain tissues from AD patients showed elevated levels of ER stress markers, such as PERK, eIF2α, IRE1α, the chaperone Grp78, and the downstream mediator of cell death CHOP. Apoptosis is in charge of eliminating unnecessary and undesired cells to maintain good health. However, it has been demonstrated that a malfunctioning apoptotic pathway is a major factor in the development of certain neurological and immunological problems and diseases in people, including neurodegenerative diseases. This article highlights and discussed some of the experimentally established mechanisms through which these processes lead to the development as well as the exacerbation of AD.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- endoplasmic reticulum
- cell death
- oxidative stress
- cell cycle arrest
- reactive oxygen species
- mental health
- end stage renal disease
- dna damage
- white matter
- public health
- cognitive decline
- chronic obstructive pulmonary disease
- newly diagnosed
- resting state
- chronic kidney disease
- healthcare
- spinal cord
- peritoneal dialysis
- inflammatory response
- prognostic factors
- amino acid
- gene expression
- protein protein
- ischemia reperfusion injury
- binding protein
- spinal cord injury
- cerebral ischemia
- intensive care unit
- small molecule
- heat shock
- social media
- signaling pathway
- brain injury