Journal of the Chemical Society, Dalton Transactions, 1993
Thermodynamic and Spectroscopic Characterization - and in vifro 0, Scavenger Activity of Copper(i... more Thermodynamic and Spectroscopic Characterization - and in vifro 0, Scavenger Activity of Copper(ii) G lycyl-L-hist idyl-g lycyl-L-histidine Complexes * ... Raffaele P. Bonomo,a Francesca Bonsignore,b Enrico Conte,a Giuseppe Impellizzeri,a Giuseppe Pappalardo,b Roberto ...
Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory gang... more Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among several models of NGF activity, the clonal cell line PC12 is the most widely employed. Thus, in the presence of NGF, through the activation of the transmembrane protein TrkA, these cells undergo a progressive mitotic arrest and start to grow electrically excitable neuritis. A vast number of studies opened intriguing aspects of NGF mechanisms of action, its biological properties, and potential use as therapeutic agents. In this context, identifying and utilizing small portions of NGF is of great interest and involves several human diseases including Alzheimer's disease. Here we report the specific action of the peptide encompassing the 1-14 sequence of the human NGF (NGF(1...
To date mainly simple complexes of divalent metal ions with nucleotides have been studied in ~olu... more To date mainly simple complexes of divalent metal ions with nucleotides have been studied in ~olution.~-~ Only recently have M"-Nu (Nu = nucleotide) complexes with biofunctional ligands been reported?+ In fact there is evidence of involve-ment of these mixed complexes in ...
Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic... more Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity ...
Homocarnosine is an endogenous dipeptide distributed in cerebral regions and cerebrospinal fluid.... more Homocarnosine is an endogenous dipeptide distributed in cerebral regions and cerebrospinal fluid. Homocarnosine may serve as an antioxidant, free radical scavenger, neurotransmitter, buffering system and metal chelating agent, especially for copper(II) and zinc(II). The homeostasis of homocarnosine is regulated by carnosinases; the serum-circulating isoform of these metallodipeptidases partially hydrolyses homocarnosine in the blood. The enzyme activity is also inhibited by homocarnosine itself in a dose-dependent manner. We synthesized a new multifunctional homocarnosine derivative with trehalose, a disaccharide that possesses several beneficial properties, among which the inhibition of protein aggregation (i.e. Aβ amyloid and polyglutamine proteins) involved in widespread neurodegenerative disorders. We studied the copper(II) binding features of the new conjugate by means of potentiometric and spectroscopic techniques (UV-visible and circular dichroism) and the superoxide dismutas...
The number of original research articles, review articles, book chapters, and monographs publishe... more The number of original research articles, review articles, book chapters, and monographs published annually on prion is staggering. The experienced reader in this field might ask: “Do we really need another review on prion protein?” This chapter attempts to be different from other recent reviews by focusing on the chemical aspects of metal binding of prion and some of its peptide fragments, rather than the biochemical and biomedical aspects, which have been covered extensively elsewhere [1–4]. A treatment of the fundamental chemistry should provide a framework for a better understanding of prion function.
The international journal of biochemistry & cell biology, Jan 14, 2015
Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent angiogenesis stimulat... more Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent angiogenesis stimulator that interacts with endothelial cells inducing a wide range of responses. Metal ions dyshomeostasis play a fundamental role in the onset of neurodegenerative diseases, in particular copper that is also involved in angiogenesis processes. It is known that vascular pathologies are present in neurodegenerative diseases and Angiogenin is down-regulated in Alzheimer and Parkinson diseases, as well as it has been found as one of the mutated genes in amyotrophic lateral sclerosis (ALS). Copper (II) induces an increase of Angiogenin binding to endothelial cells but, so far, the relationship between copper-ANG and angiogenesis induction remain unclear. Herein, the effects of copper (II) ions on Angiogenin activity and expression were evaluated. The binding of copper was demonstrated to affect the intracellular localization of the protein decreasing its nuclear translocation. Moreover, the ANG-...
... Printed in The Netherlands A COMPUTER METHOD FOR THE CALCULATION OF ENTHALPY CHANGES FOR ION ... more ... Printed in The Netherlands A COMPUTER METHOD FOR THE CALCULATION OF ENTHALPY CHANGES FOR ION ASSOCIATION IN SOLUTION FIRM CALORIMETRIC DATA CARMELO RIGANO Seminario ... 12 JJ Christensen, DP Wrathall, JO Oscarson and RM Izatt, Anal. ...
The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathog... more The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Abeta peptides (Lambert et al., 1998) indicate that self-association of Abeta(1-42) monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Abeta(1-42) is unknown. The evidence that Abeta(1-42) is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Abeta(1-42) monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Abeta(1-42) monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3-kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Abeta(1-42) carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Abeta(1-42) may also cause neurodegeneration by depriving neurons of the protective activity of Abeta(1-42) monomers. This "loss-of-function" hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Abeta burden.
Journal of the Chemical Society, Dalton Transactions, 1993
Thermodynamic and Spectroscopic Characterization - and in vifro 0, Scavenger Activity of Copper(i... more Thermodynamic and Spectroscopic Characterization - and in vifro 0, Scavenger Activity of Copper(ii) G lycyl-L-hist idyl-g lycyl-L-histidine Complexes * ... Raffaele P. Bonomo,a Francesca Bonsignore,b Enrico Conte,a Giuseppe Impellizzeri,a Giuseppe Pappalardo,b Roberto ...
Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory gang... more Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among several models of NGF activity, the clonal cell line PC12 is the most widely employed. Thus, in the presence of NGF, through the activation of the transmembrane protein TrkA, these cells undergo a progressive mitotic arrest and start to grow electrically excitable neuritis. A vast number of studies opened intriguing aspects of NGF mechanisms of action, its biological properties, and potential use as therapeutic agents. In this context, identifying and utilizing small portions of NGF is of great interest and involves several human diseases including Alzheimer's disease. Here we report the specific action of the peptide encompassing the 1-14 sequence of the human NGF (NGF(1...
To date mainly simple complexes of divalent metal ions with nucleotides have been studied in ~olu... more To date mainly simple complexes of divalent metal ions with nucleotides have been studied in ~olution.~-~ Only recently have M"-Nu (Nu = nucleotide) complexes with biofunctional ligands been reported?+ In fact there is evidence of involve-ment of these mixed complexes in ...
Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic... more Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity ...
Homocarnosine is an endogenous dipeptide distributed in cerebral regions and cerebrospinal fluid.... more Homocarnosine is an endogenous dipeptide distributed in cerebral regions and cerebrospinal fluid. Homocarnosine may serve as an antioxidant, free radical scavenger, neurotransmitter, buffering system and metal chelating agent, especially for copper(II) and zinc(II). The homeostasis of homocarnosine is regulated by carnosinases; the serum-circulating isoform of these metallodipeptidases partially hydrolyses homocarnosine in the blood. The enzyme activity is also inhibited by homocarnosine itself in a dose-dependent manner. We synthesized a new multifunctional homocarnosine derivative with trehalose, a disaccharide that possesses several beneficial properties, among which the inhibition of protein aggregation (i.e. Aβ amyloid and polyglutamine proteins) involved in widespread neurodegenerative disorders. We studied the copper(II) binding features of the new conjugate by means of potentiometric and spectroscopic techniques (UV-visible and circular dichroism) and the superoxide dismutas...
The number of original research articles, review articles, book chapters, and monographs publishe... more The number of original research articles, review articles, book chapters, and monographs published annually on prion is staggering. The experienced reader in this field might ask: “Do we really need another review on prion protein?” This chapter attempts to be different from other recent reviews by focusing on the chemical aspects of metal binding of prion and some of its peptide fragments, rather than the biochemical and biomedical aspects, which have been covered extensively elsewhere [1–4]. A treatment of the fundamental chemistry should provide a framework for a better understanding of prion function.
The international journal of biochemistry & cell biology, Jan 14, 2015
Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent angiogenesis stimulat... more Angiogenin (ANG), a member of the secreted ribonuclease family, is a potent angiogenesis stimulator that interacts with endothelial cells inducing a wide range of responses. Metal ions dyshomeostasis play a fundamental role in the onset of neurodegenerative diseases, in particular copper that is also involved in angiogenesis processes. It is known that vascular pathologies are present in neurodegenerative diseases and Angiogenin is down-regulated in Alzheimer and Parkinson diseases, as well as it has been found as one of the mutated genes in amyotrophic lateral sclerosis (ALS). Copper (II) induces an increase of Angiogenin binding to endothelial cells but, so far, the relationship between copper-ANG and angiogenesis induction remain unclear. Herein, the effects of copper (II) ions on Angiogenin activity and expression were evaluated. The binding of copper was demonstrated to affect the intracellular localization of the protein decreasing its nuclear translocation. Moreover, the ANG-...
... Printed in The Netherlands A COMPUTER METHOD FOR THE CALCULATION OF ENTHALPY CHANGES FOR ION ... more ... Printed in The Netherlands A COMPUTER METHOD FOR THE CALCULATION OF ENTHALPY CHANGES FOR ION ASSOCIATION IN SOLUTION FIRM CALORIMETRIC DATA CARMELO RIGANO Seminario ... 12 JJ Christensen, DP Wrathall, JO Oscarson and RM Izatt, Anal. ...
The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathog... more The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Abeta peptides (Lambert et al., 1998) indicate that self-association of Abeta(1-42) monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Abeta(1-42) is unknown. The evidence that Abeta(1-42) is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Abeta(1-42) monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Abeta(1-42) monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3-kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Abeta(1-42) carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Abeta(1-42) may also cause neurodegeneration by depriving neurons of the protective activity of Abeta(1-42) monomers. This "loss-of-function" hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Abeta burden.
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Papers by Enrico Rizzarelli