The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis

Abstract

. The importance of His84 of NGF for transition metal cation binding is demonstrated, con®rming the involvement of this residue in metal ion coordination.

The inorganic perspectives of neurotrophins and Alzheimer's disease

“…Thus, it has been suggested that the binding of metals is responsible for the alteration of NGF conformation and, in turn, for the inhibition of its biological activities [116]. Also, computational approaches have been carried out to investigate the interaction of NGF with other transition metal ions [132,133]. It is interesting to note that copper(II) ion has been reported to be the only metal ion able to bind the imidazole nitrogen stronger than a proton at pH values higher than 6-6,5.…”

“…It is interesting to note that copper(II) ion has been reported to be the only metal ion able to bind the imidazole nitrogen stronger than a proton at pH values higher than 6-6,5. At lower pH values, the imidazole is unable to coordinate Cu 2 + [133]. Moreover, it has been proposed that NGF might interact with its receptors as a complex with zinc(II) ion [116,131].…”

Mechanisms of disease

“…TrkA receptors can be transactivated by activated G-protein coupled receptor (GPCR) signaling pathways. Beyond GPCR transactivation of TrkA, there are other compounds such as copper and zinc that can activate TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins (Hwang et al, 2007;Huang et al, 2008) with the potential caveat that zinc has also been shown to induce conformational changes in neurotrophins that impair their ability to activate their receptors (Ross et al, 1997;Ross et al, 2001;Post et al, 2008). VERGE ET AL.…”

Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for Neurotrophic Factors and Metals Link

“…Metabolic dysfunction of NGF is involved in Alzheimer’s Diseases (AD) occurrence [9,10,11]. Metal ions play a role in AD [12,13,14] and copper and zinc ions can modulate NGF activity in the same brain areas affected by metal dyshomeostasis in pathological conditions [15,16,17]. Metal binding can induce NGF conformational changes that hinder the recognition process with its cellular receptors [18,19,20].…”