α-MSH Peptides Inhibit Production of Nitric Oxide and Tumor Necrosis Factor-α by Microglial Cells Activated with β-Amyloid and Interferon γ

Galimberti, Daniela; Baron, Pierluigi; Meda, Lucia; Prat, Elisabetta; Scarpini, Elio; Delgado, René; Catania, Anna; Scarlato, G.

doi:10.1006/bbrc.1999.1276

Cited by 79 publications

(61 citation statements)

References 28 publications

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“…Control animals were infused with the nontoxic reverse fragment Ab40-1. Accumulation of Ab in the hippocampus was demonstrated immunohistochemially with anti-Ab (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) antibodies, but no Congo red birefringence was observed. 21 AG (100 mg/kg, i.p.)…”

Section: Animals and Drug Treatmentsmentioning

confidence: 97%

“…[1][2][3][4][5][6][7] It has been demonstrated that aggregation of Ab can attract inflammatory mediators 8,9 which, in turn, generate NO radicals. 10 We have previously demonstrated that continuous intracerebroventricular infusion of Ab induced a time-dependent expression of iNOS in the hippocampus and that treatment with specific inhibitors for iNOS ameliorated Ab-induced impairment of nicotine-evoked ACh release and spatial memory deficits.…”

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confidence: 99%

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Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction

et al. 2003

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Amyloid b (Ab) is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). We have previously demonstrated that continuous intracerebroventricular infusion of Ab1-40 induced a time-dependent expression of the inducible nitric oxide (NO) synthase (iNOS) and an overproduction of NO in the rat hippocampus. The pathophysiological significance of the overproduction of NO on brain function was manifested by an impairment of nicotine-evoked acetylcholine(ACh) release and memory deficits. 4 Molecular mechanisms by which NO participates in the Ab-induced brain dysfunction, however, remain to be determined. Here we show that chronic Ab1-40 infusion caused a robust peroxynitrite formation and subsequent tyrosine nitration of proteins in the hippocampus. Immunoprecipitation and Western blot analyses further revealed that synaptophysin, a synaptic protein, was a main target of tyrosine nitration. Chronic infusion of Ab1-40 resulted in an impairment of nicotine-evoked ACh release as analyzed by microdialysis. Daily treatment with the iNOS inhibitor aminoguanidine (AG) or the peroxynitrite scavenger uric acid (UA) prevented the tyrosine nitration of synaptophysin as well as the impairment of nicotine-evoked ACh release induced by Ab. Our findings suggest that the tyrosine nitration of synaptophysin is related to Ab-induced impairment of ACh release.

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Section: Animals and Drug Treatmentsmentioning

confidence: 97%

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confidence: 99%

Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction

et al. 2003

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“…Microglial apoptosis ( duced production of NO and TNFa, 110) and melatonin inhibits Ab-induced production of IL-1b and IL-6 in brain slices. 111) 4.7.…”

Section: Opioids and Their Antagonistsmentioning

confidence: 99%

Regulating Factors for Microglial Activation.

Nakamura

2002

Biological & Pharmaceutical Bulletin

223

114

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“…A number of in vitro studies have demonstrated that A␤ fibril stimulation increases microglial tumor necrosis factor ␣ (TNF␣) production (Klegeris et al, 1997;Galimberti et al, 1999;Tan et al, 2000;Combs et al, 2001). Although TNF␣ has been described as a neuronal anti-apoptotic agent (Barger et al, 1995;Gary et al, 1998;Glazner and Mattson, 2000), it is also capable of inducing neuronal death when presented to neurons as part of a glialderived inflammatory milieu (Gelbard et al, 1993;Chao and Hu, 1994;Venters et al, 1999;Combs et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

β-Amyloid-Stimulated Microglia Induce Neuron Death via Synergistic Stimulation of Tumor Necrosis Factor α and NMDA Receptors

Floden¹,

Li²,

Combs³

2005

J. Neurosci.

224

158

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Although abundant reactive microglia are found associated with ␤-amyloid (A␤) plaques in Alzheimer's disease (AD) brains, their contribution to cell loss remains speculative. A variety of studies have documented the ability of A␤ fibrils to directly stimulate microglia in vitro to assume a neurotoxic phenotype characterized by secretion of a plethora of proinflammatory molecules. Collectively, these data suggest that activated microglia play a direct role in contributing to neuron death in AD rather than simply a role in clearance after plaque deposition. Although it is clear the A␤-stimulated microglia acutely secrete toxic oxidizing species, the identity of longer-lived neurotoxic agents remains less defined. We used A␤-stimulated conditioned media from primary mouse microglia to identify more stable neurotoxic secretions. The NMDA receptor antagonists memantine and 2-amino-5-phosphopetanoic acid as well as soluble tumor necrosis factor ␣ (TNF␣) receptor protect neurons from microglial-conditioned media-dependent death, implicating the excitatory neurotransmitter glutamate and the proinflammatory cytokine TNF␣ as effectors of microglial-stimulated death. Neuron death occurs in an oxidative damage-dependent manner, requiring activity of inducible nitric oxide synthase. Toxicity results from coincident stimulation of the TNF␣ and NMDA receptors, because stimulations of either alone are insufficient to initiate cell death. These findings suggest the hypothesis that AD brains provide the appropriate microglial-mediated inflammatory environment for TNF␣ and glutamate to synergistically stimulate toxic activation of their respective signaling pathways in neurons as a contributing mechanism of cell death.

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α-MSH Peptides Inhibit Production of Nitric Oxide and Tumor Necrosis Factor-α by Microglial Cells Activated with β-Amyloid and Interferon γ

Cited by 79 publications

References 28 publications

Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction

Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid β-peptide-induced cholinergic dysfunction

Regulating Factors for Microglial Activation.

β-Amyloid-Stimulated Microglia Induce Neuron Death via Synergistic Stimulation of Tumor Necrosis Factor α and NMDA Receptors

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