Oxidative Stress and Cognitive Impairment in Neurodegenerative Disorders

Oxidative stress arises when the generation of reactive oxygen species (ROS) outpaces endogenous antioxidant defences, leading to damage of lipids, proteins and nucleic acids. In the ageing brain and in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, oxidative imbalance is intertwined with mitochondrial dysfunction, protein aggregation and chronic neuroinflammation. Neuronal populations with high metabolic demand are especially vulnerable to redox disruption, which can impair synaptic transmission, reduce neurotrophic support and trigger apoptotic pathways. Accumulation of misfolded proteins such as amyloid-β and phosphorylated tau further exacerbates ROS production, creating a self-reinforcing cycle of oxidative injury and cognitive decline. Emerging research highlights the central role of transcriptional regulators of antioxidant defences, the impact of endoplasmic reticulum stress and the cross-talk between glial cells and neurons in modulating disease progression. A deeper understanding of these mechanisms underpins the development of targeted interventions that bolster endogenous redox capacity, stabilise mitochondrial function and preserve synaptic integrity.

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Oxidative Stress and Cognitive Impairment in Neurodegenerative Disorders publication trend

The graph below shows the total number of articles in oxidative stress and cognitive impairment in neurodegenerative disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: Imbalance between the production of reactive oxygen species and the capacity of antioxidant defences, leading to cellular damage.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can oxidise biomolecules and disrupt cellular function.

Nrf2: Nuclear transcription factor that orchestrates the expression of antioxidant and cytoprotective genes in response to oxidative challenge.

Endoplasmic reticulum stress: Cellular condition arising from accumulation of unfolded proteins in the endoplasmic reticulum, often linked to disrupted protein homeostasis and oxidative damage.

References

1. Caffeic Acid, a Polyphenolic Micronutrient Rescues Mice Brains against Aβ-Induced Neurodegeneration and Memory Impairment. Antioxidants (2023).
2. Neuromodulatory effect of vardenafil on aluminium chloride/d-galactose induced Alzheimer’s disease in rats: emphasis on amyloid-beta, p-tau, PI3K/Akt/p53 pathway, endoplasmic reticulum stress, and cellular senescence. Inflammopharmacology (2023).
3. Fisetin Rescues the Mice Brains Against D-Galactose-Induced Oxidative Stress, Neuroinflammation and Memory Impairment. Frontiers in Pharmacology (2021).