The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases

Abstract

Iron accumulation in the brain is a common feature of many neurodegenerative diseases. Its involvement spans across the main proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. Accumulating evidence supports the contribution of iron in disease pathologies, but the delineation of its pathogenic role is yet challenged by the complex involvement of iron in multiple neurotoxicity mechanisms and evidence supporting a reciprocal influence between accumulation of iron and protein pathology. Here, we review the major proteinopathy-specific observations supporting four distinct hypotheses: (1) iron deposition is a consequence of protein pathology; (2) iron promotes protein pathology; (3) iron protects from or hinders protein pathology; and (4) deposition of iron and protein pathology contribute parallelly to pathogenesis. Iron is an essential element for physiological brain function, requiring a fine balance of its levels. Understanding of disease-related iron accumulation at a more intricate and systemic level is critical for advancements in iron chelation therapies.

Migration Patterns and Potential Risk Assessment of Trace Elements in the Soil–Plant System in the Production Area of the Chinese Medicinal Herb Scrophularia ningpoensis Hemsl.

“…It has been shown that moderate concentrations of zinc can improve seed germination, but high concentrations of zinc can inhibit plant growth [6]. Moderate amounts of iron can prevent or hinder protein pathology [7]. When manganese is deficient in animals, it interferes with normal growth rates [8].…”