Oxidative Stress and Cellular Senescence in Alzheimer's Disease

In this paper, the authors discuss the overlap between oxidative stress and growing numbers of senescent cells in the brain. Both are thought to contribute to neurodegenerative conditions such as Alzheimer's disease. The aging of the brain is complex, a web of interacting processes, causes, and consequences. It has proven to be difficult to determine which processes are more or less important; the only efficient way forward is to come up with interventions that remove just one contributing factor with minimal side-effects. That is now possible for senescent cells, and clinical trials are underway, but manipulation of oxidative stress without changing other factors is a much more challenging prospect.

The redox process and cellular senescence are involved in a range of essential physiological functions. However, they are also implicated in pathological processes underlying age-related neurodegenerative disorders, including Alzheimer's disease (AD). Elevated levels of reactive oxygen species (ROS) are generated as a result of abnormal accumulation of beta-amyloid peptide (Aβ), tau protein, and heme dyshomeostasis and is further aggravated by mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Excessive ROS damages vital cellular components such as proteins, DNA, and lipids. Such damage eventually leads to impaired neuronal function and cell death.

Heightened oxidative stress can also induce cellular senescence via activation of the senescence-associated secretory phenotype to further exacerbate inflammation and tissue dysfunction. In this review, we focus on how changes in the redox system and cellular senescence contribute to AD and how they are affected by perturbations in heme metabolism and mitochondrial function. While potential therapeutic strategies targeting such changes have received some attention, more research is necessary to bring them into clinical application.

Link: https://doi.org/10.1016/j.redox.2024.103048

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