Cognitive Dysfunction in Parkinson’s Disease: Hippocampal Vulnerability and Redox-Driven Mechanisms
Redox Mechanisms of Cognitive Decline
Cognitive decline remains one of the greatest unmet needs in Parkinson’s disease. Many patients progress from mild cognitive impairment to Parkinson’s disease dementia, and this progression carries a heavy cost to their independence and quality of life. Despite that burden, the options available today remain largely symptomatic, as dopaminergic therapies have limited impact on cognition and cholinesterase inhibitors bring only modest benefit without touching the underlying disease process.
Our recent review in Redox Biology sets out to address this gap by examining the mechanisms behind cognitive decline and placing the hippocampus at the centre of disease vulnerability. Neurotransmitter deficits, protein aggregation, oxidative stress and neuroinflammation have long been studied as separate processes, and what the review brings together is the evidence showing how they converge to drive progressive cognitive dysfunction.
Within that convergence, Nox4 emerges as a key regulator. Elevated activity of this NADPH oxidase isoform is increasingly linked to neuroinflammation, protein aggregation and hippocampal dysfunction, whereas its selective inhibition preserves neuronal integrity and improves cognitive performance in preclinical models.
Together, these insights shape the direction of our work at NeuroSoV. By targeting Nox4-driven oxidative stress, we address the disease at its source, pursuing a disease-modifying strategy rather than symptom management.