The tachykinin peptide neurokinin B binds copper(I) and silver(I) and undergoes quasi-reversible electrochemistry: Towards a new function for the peptide in the brain

Grosas, Aidan B.; Kalimuthu, Palraj; Smith, A.C.; Williams, Peter A.; Millar, Thomas J.; Bernhardt, Paul V.; Jones, Christopher E.

doi:10.1016/j.neuint.2014.03.002

Cited by 15 publications

(17 citation statements)

References 47 publications

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“…1). Accordingly, this peptide was shown to bind copper in both the Cu 2+ and Cu + oxidation states, although the Cu(II) coordination is less well established than the Cu(I) coordination (Russino et al, 2013;Grosas et al, 2014). It was…”

Section: Copper Binding To Gnrh-i and Nkb Modifies The Structure And mentioning

confidence: 99%

Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction

Peacey

Elphick

Jones

2020

General and Comparative Endocrinology

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Copper is a metal ion present in all organisms, where it has well-known roles in association with proteins and enzymes essential for cellular processes. In the early decades of the twentieth century copper was shown to influence mammalian reproductive biology, and it was subsequently shown to exert effects primarily at the level of the pituitary gland and/or hypothalamic regions of the brain. Furthermore, it has been reported that copper can interact with key neuropeptides in the hypothalamic-pituitary-gonadal axis, notably gonadotropinreleasing hormone (GnRH) and neurokinin B. Interestingly, recent phylogenetic analysis of the sequences of GnRH-related peptides indicates that copper binding is an evolutionarily ancient property of this neuropeptide family, which has been variously retained, modified or lost in the different taxa. In this mini-review the metal-binding properties of neuropeptides in the vertebrate reproductive pathway are reviewed and the evolutionary and functional significance of copper binding by GnRH-related neuropeptides in vertebrates and invertebrates are discussed.

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Section: Copper Binding To Gnrh-i and Nkb Modifies The Structure And mentioning

confidence: 99%

Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction

Peacey

Elphick

Jones

2020

General and Comparative Endocrinology

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“…Besides changes in charge, the ionic radii of Ag(I) and divalent metal ions differ, together with small deviations in preferred binding ligands and coordination geometry (Table S1). Both in vitro and in vivo studies showed Cu(I) replacement by Ag(I) ions in copper-containing proteins (37)(38)(39). Ag(I) ions exhibit a larger Pauling radius and a smaller charge density than Cu(I) ions (Table S1), but due to the same electric charge number the more stable Ag(I) ions have been used as a probe for the readily redox-active Cu(I) ions in in vitro studies (40)(41)(42).…”

Section: ________________________________________mentioning

confidence: 99%

Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation–inert complex

Wallin

Jarvet

Biverstål

et al. 2020

Journal of Biological Chemistry

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A detailed understanding of the molecular pathways for amyloid-β (Aβ) peptide aggregation from monomers into amyloid fibrils, a hallmark of Alzheimer's disease, is crucial for the development of diagnostic and therapeutic strategies. We investigate the molecular details of peptide fibrillization in vitro by perturbing this process through addition of differently charged metal ions. Here, we used a monovalent probe, the silver ion, that, similarly to divalent metal ions, binds to monomeric Aβ peptide and efficiently modulates Aβ fibrillization. On the basis of our findings, combined with our previous results on divalent zinc ions, we propose a model that links the microscopic metal-ion binding to Aβ monomers to its macroscopic impact on the peptide self-assembly observed in bulk experiments. We found that substoichiometric concentrations of the investigated metal ions bind specifically to the N-terminal region of Aβ, forming a dynamic, partially compact complex. The metal-ion bound state appears to be incapable of aggregation, effectively reducing the available monomeric Aβ pool for incorporation into fibrils. This is especially reflected in a decreased fibril-end elongation rate. However, because the bound state is significantly less stable than the amyloid state, Aβ peptides are only transiently redirected from fibril formation, and eventually almost all Aβ monomers are integrated into fibrils. Taken together, these findings unravel the mechanistic consequences of delaying Aβ aggregation via weak metal-ion binding, quantitatively linking the contributions of specific interactions of metal ions with monomeric Aβ to their effects on bulk aggregation.

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“…It is known that the dysfunction of metal ions, such as copper is a feature of Alzheimer's disease. Neurokinin B protects against copper-induced calcium channel opening (Russino et al, 2013), as well as the synaptic homeostasis (Grosas et al, 2014).…”

Section: Substance P and Alzheimer's Diseasementioning

confidence: 99%

Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease

Chen

2019

Front. Mol. Neurosci.

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Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits and neuronal loss. Deposition of beta-amyloid peptide (Aβ) causes neurotoxicity through the formation of plaques in brains of Alzheimer's disease. Numerous studies have indicated that the neuropeptides including ghrelin, neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y, substance P and orexin are closely related to the pathophysiology of Alzheimer's disease. The levels of neuropeptides and their receptors change in Alzheimer's disease. These neuropeptides exert neuroprotective roles mainly through preventing Aβ accumulation, increasing neuronal glucose transport, increasing the production of neurotrophins, inhibiting endoplasmic reticulum stress and autophagy, modulating potassium channel activity and hippocampal long-term potentiation. Therefore, the neuropeptides may function as potential drug targets in the prevention and cure of Alzheimer's disease.

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The tachykinin peptide neurokinin B binds copper(I) and silver(I) and undergoes quasi-reversible electrochemistry: Towards a new function for the peptide in the brain

Cited by 15 publications

References 47 publications

Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction

Roles of copper in neurokinin B and gonadotropin-releasing hormone structure and function and the endocrinology of reproduction

Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation–inert complex

Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease

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