Alberto Chiarugi

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High mobility group proteins are chromatin binding factors with key roles in maintenance of nuclear homeostasis. The evidence indicates that extracellularly released high mobility group box 1 (HMGB1) protein behaves as a cytokine, promoting inflammation and participating to the pathogenesis of several disorders in peripheral organs. In this study, we have(More)
Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c release and caspase 8 substrate, was expressed in brain, activated after an ischemic insult in vivo and in vitro, and contributed to ischemic cell death. We(More)
Poly(ADP-ribose) polymerase 1 (PARP-1) is an abundant nuclear enzyme involved in DNA repair. The therapeutic efficacy of drugs that inhibit PARP-1 in various disorders underscores the active role of PARP-1 in cell death. Although it is well established that excessive DNA damage causes PARP-1 hyperactivation, which leads to cell death by energy failure, a(More)
NAD is a vital molecule in all organisms. It is a key component of both energy and signal transduction--processes that undergo crucial changes in cancer cells. NAD(+)-dependent signalling pathways are many and varied, and they regulate fundamental events such as transcription, DNA repair, cell cycle progression, apoptosis and metabolism. Many of these(More)
Pharmacological manipulation of gene expression is considered a promising avenue to reduce postischemic brain damage. Histone deacetylases (HDACs) play a central role in epigenetic regulation of transcription, and inhibitors of HDACs are emerging as neuroprotective agents. In this study, we investigated the effect of the HDAC inhibitor suberoylanilide(More)
Several kynurenine analogues were synthesized and tested as inhibitors of the enzymes kynurenine hydroxylase and/or kynureninase with the aim of identifying new compounds able to inhibit the synthesis of quinolinic acid (an endogenous excitotoxin) and to increase that of kynurenic acid, an endogenous antagonist of ionotropic glutamate receptors. Among these(More)
An excessive activation of poly(ADP-ribose) polymerase (PARP) has been proposed to play a key role in post-ischemic neuronal death. We examined the neuroprotective effects of the PARP inhibitors benzamide, 6(5H)-phenanthridinone, and 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinone in three rodent models of cerebral ischemia. Increasing(More)
Excessive release of proinflammatory products by activated glia causes neurotoxicity and participates in the pathogenesis of neurodegenerative disorders. Recently, poly(ADP-ribose) polymerase-1 (PARP-1) has been shown to play a key role in nuclear factor kappa B (NF-kappaB)-driven expression of inflammatory mediators by glia during the neuroimmune response.(More)
In 1996, Wang and his group empirically disclosed a key role of (deoxy)-ATP in functioning of the apoptotic machinery. After almost a decade, and despite the emerged intricacy of the death pathways, ATP is still considered a key determinant of apoptosis with no apparent active roles in necrosis. Yet recent findings indicate that apoptosis proceeds even(More)
Upon massive DNA damage, hyperactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 causes severe depletion of intracellular NAD and ATP pools as well as mitochondrial dysfunction. Thus far, the molecular mechanisms contributing to PARP-1-dependent impairment of mitochondrial functioning have not been identified. We found that degradation of(More)