NeuralCipher Research overview
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"Sola dosis facit venenum" (Paracelsus). Essential trace elements, crucial for maintaining neuronal function, have their dysregulation increasingly correlated with neurodegenerative disorders, particularly Parkinson's disease (PD). This systematic review aims to synthesize recent high-quality evidence regarding the involvement of essential trace elements, such as iron, zinc, copper, manganese, and selenium, in the pathogenesis and, consequently, as potential therapeutic targets of PD. A comprehensive literature search was conducted for articles published between 1 January 2023 and 31 December 2024. Out of an initial pool of 1231 identified studies, 63 met the methodological eligibility criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All potentially eligible interventional and observational studies were initially assessed using the Physiotherapy Evidence Database (PEDro) scale, which is commonly employed for evaluating the internal validity and statistical interpretability of clinical trials and rehabilitation-focused studies. Following the qualitative assessment using the PEDro scale, 18 studies were ultimately selected based on their scientific relevance and methodological rigor. To supplement the PEDro scoring, which is designed primarily for individual trials, we applied the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist for the evaluation of the included systematic reviews or meta-analyses. The included studies employed a variety of clinical, postmortem, and experimental models to investigate trace-element concentrations and their mechanistic roles in PD. The findings revealed consistent patterns of iron accumulation in the substantia nigra, zinc's bidirectional effects on oxidative stress and autophagy, copper-induced α-synuclein aggregation, and the neuroprotective role of selenium via antioxidant pathways. Manganese was associated with mitochondrial dysfunction and neuroinflammation. Essential trace-element disturbances contribute to PD pathology through interconnected mechanisms involving redox imbalance, protein misfolding, and impaired cellular homeostasis. These elements may serve as both biomarkers and potential therapeutic tools, warranting further investigation into personalized metal-based interventions for PD.
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