Comprehensive Summary
Serban et. al discusses the role of oxidative stress in neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis(ALS). The authors analyzed preclinical and clinical trial data, biomarker profiling, therapeutic trials, and multi-omics. They examine the impact of reactice oxygen species and nitrogen species on mitochondrial, lipid, protein, and DNA damage by feedback loop, which eventually accelerates neurodegeneration. The role of the biomarkers carbonylated tau, nitrated a-synuclein, 4-HNE, and 8-OHdG were also emphasized within the disease progression. The authors also study mitochondria-targeted antioxidant trials, NrF2 activators, nanoparticle drug delivery, CRISPR gene editing, and epigenetic reprogramming. Overall, the authors state that single-agent antioxidant therapies are inadequate as interventions, and more multi-targeted interventions will shape the future of redox medications.
Outcomes and Implications
This study is critical as it shows that oxidative stress is a modifiable driver of neurodegeneration. The findings show that next-generation therapies must be multi-strategic, like the mitochondria-directed antioxidants with Nrf2 activators or nanomedicine based delivery systems. This AI driven biomarker discovery could lead to tailored treatment plans, which could then move towards management of symptoms and disease reversal in the next decade.