Amyloid beta-metal ion complex (Aβ-metal complex)

The **amyloid beta-metal ion complex** refers to the molecular assemblies formed when amyloid beta peptide (Aβ)—particularly Aβ1-40 and Aβ1-42—binds transition metal ions such as copper (Cu), zinc (Zn), iron (Fe), and others[2][3][4][5]. These complexes are centrally involved in the pathology of Alzheimer’s disease, as metal binding profoundly affects the aggregation, structural forms, and neurotoxic properties of Aβ. Metal interactions modulate the conformational state and aggregation kinetics of Aβ, typically stabilizing certain structures and influencing the transition between monomer, oligomer, and fibril states[1][2][3]. At low metal ion concentrations, binding can inhibit fibril formation and favor non-aggregated or amorphous forms, while at higher concentrations, abnormal and often toxic aggregates may form[2][3][4]. The metal-bound “folded” state is often in dynamic equilibrium with “unfolded” peptide, impacting the generation of neurotoxic Aβ oligomers[2][3]. Metal-Aβ complexes also contribute to oxidative stress and play a role in synaptic dysfunction and neuronal cell death associated with Alzheimer’s disease[6][4]. Therapeutic approaches include metal chelation and use of metal-binding drugs to disrupt these complexes, with several experimental and investigational drugs targeting this interaction[7]. Targeting amyloid beta-metal ion complex presents challenges such as preserving physiological metal balance while mitigating neurotoxicity[6].

Other names

Amyloid-β-metal complexAβ-metal complexAmyloid beta-metal interactionAmyloid-β-metal ion complexMetal-bound amyloid beta peptide

Inhibition of amyloid beta aggregation by metal chelation or sequestration; Disruption of toxic oligomer/fibril formation; Modulation of peptide conformation and self-assembly dynamics