Cadmium-Induced Toxicity as a Pathophysiological Mechanism for Parkinson's Disease Onset in Individuals with Iron and Zinc Deficiencies and Chronic Obstructive Pulmonary Disease.

The pathophysiological basis of Parkinson's disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson's disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson's disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency-known risk factors for Parkinson's disease-lead to an increased cadmium burden and contribute to the onset and progression of the disease.