Research on the Imbalance of Metal Homeostasis and Ferroptosis Mechanisms in Neurodegenerative Diseases

To investigate the associations between urinary and serum metal levels and neurodegenerative diseases (NGDs) as well as all-cause mortality, and identify research trends through bibliometric. This study first analyzed data from a large-scale national cross-sectional survey (2005–2018) involving 6,288 participants. Multivariable regression models were used to assess the associations of urinary metals (Ba, Cd, Co, Cs, Mo, Pb, Sb, Tl, W) and serum metals (Fe, Cd, Pb, Hg) with the risk of neurodegenerative diseases (NGDs) and all-cause mortality. Subsequently, a bibliometric analysis was conducted on literature pertaining to "metals" and "NGDs" retrieved from the Web of Science Core Collection to identify research trends and key underlying mechanisms. Epidemiological analyses revealed significant associations between several metals—such as Cd, Cs, Mo, Hg, and Pb—and either NGDs risk or all-cause mortality, with some exhibiting nonlinear patterns ( e.g. L-shaped or inverted U-shaped relationships). Subsequent bibliometric analysis of 34,313 publications identified "iron" as a central hub keyword linking "metal exposure" to "neurodegenerative diseases". Mechanisms related to Fe—including "oxidative stress" and "lipid peroxidation"—emerged as research hotspot keywords. Notably, the cluster labeled "ferroptosis" demonstrated substantial scale in co-citation clustering. Research trajectories have evolved from broad pathological observations toward molecular-level investigations of the NLRP3 inflammasome, glutathione peroxidase 4 (GPX4), ultimately converged on the ferroptosis pathway. Exposure to multiple metals is significantly associated with the risk and prognosis of NGDs. Integrated bibliometric evidence highlights ferroptosis as the central mechanism bridging metal dyshomeostasis and neuronal injury, offering a cohesive evidence chain from population data to mechanistic insights.