Abstract
Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and post-stroke cognitive impairment (PSCI), represent an escalating global health and economic challenge. In the quest for disease-modifying interventions, natural polyphenols-most notably curcumin, the principal bioactive compound of Curcuma longa-have attracted considerable interest due to their pleiotropic neuroprotective effects. This narrative review critically synthesizes findings from a selection of peer-reviewed articles published between 2000 and 2025, chosen for their relevance to curcumin's molecular mechanisms and translational potential. Curcumin's complex chemical structure confers antioxidant, anti-inflammatory, and epigenetic modulatory properties; however, its clinical application is limited by poor oral bioavailability. Mechanistically, curcumin attenuates oxidative stress and suppresses key inflammatory mediators, including nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Additionally, it modulates apoptosis, inhibits amyloid-beta aggregation, and enhances cellular quality control processes such as autophagy and mitophagy, while upregulating neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Preclinical studies employing rodent models of AD, PD, and ischemic stroke have demonstrated curcumin's dose-dependent neuroprotective efficacy, with improved outcomes observed using nanoparticle-based delivery systems. Early-phase clinical trials further support curcumin's favorable safety profile and potential cognitive benefits, although challenges remain regarding pharmacokinetics, formulation standardization, and therapeutic reproducibility. Future directions include the development of advanced drug delivery platforms, combinatory therapeutic regimens, and personalized medicine approaches integrating curcumin within multifaceted neurotherapeutic strategies. Collectively, this narrative review highlights curcumin as a promising multi-targeted candidate for combating neurodegenerative diseases, while emphasizing the need for further translational and clinical validation.