Link Between Metal Homeostasis and Neurodegenerative Diseases: Crosstalk of Metals and Amyloidogenic Proteins at the Synapse

Mizuno, Dai; Kawahara, Masahiro

doi:10.1007/978-4-431-56463-8_14

Cited by 1 publication

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“…The dyshomeostasis of neurometals, in particular, iron, zinc, copper, and manganese, in various brain areas contributes to the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease (AD), prion diseases, and Parkinson’s disease (PD). − Among the possible effects ascribable to metal ions are the impairment of normal brain functions, such as neurotransmitter synthesis and neural information processing, − and the induction of conformational changes and/or aggregation of various disease-related proteins, including α-synuclein (αSyn) in PD, β-amyloid (Aβ), and τ in AD and prion protein (PrP) in prion diseases . There is an emerging link between the membrane-anchored form of cellular PrP and amyloid proteins, in their monomeric or oligomeric forms, as PrP appears to act as the binding receptor for αSyn, Aβ, and τ .…”

Section: Introductionmentioning

confidence: 99%

Membrane Binding Strongly Affecting the Dopamine Reactivity Induced by Copper Prion and Copper/Amyloid-β (Aβ) Peptides. A Ternary Copper/Aβ/Prion Peptide Complex Stabilized and Solubilized in Sodium Dodecyl Sulfate Micelles

et al. 2019

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The combination between dyshomeostatic levels of catecholamine neurotransmitters and redox-active metals such as copper and iron exacerbates the oxidative stress condition that typically affects neurodegenerative diseases. We report a comparative study of the oxidative reactivity of copper complexes with amyloid-β (Aβ 40 ) and the prion peptide fragment 76-114 (PrP 76−114 ), containing the high-affinity binding site, toward dopamine and 4-methylcatechol, in aqueous buffer and in sodium dodecyl sulfate micelles, as a model membrane environment. The competitive oxidative and covalent modifications undergone by the peptides were also evaluated. The high binding affinity of Cu/peptide to micelles and lipid membranes leads to a strong reduction (Aβ 40 ) and quenching (PrP 76−114 ) of the oxidative efficiency of the binary complexes and to a stabilization and redox silencing of the ternary complex Cu II /Aβ 40 /PrP 76−114 , which is highly reactive in solution. The results improve our understanding of the pathological and protective effects associated with these complexes, depending on the physiological environment.

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