Your search for: 'author:("Polito, Letizia")' has returned 4 results. (0.008s) Save search

Authors: Albani, Diego | Polito, Letizia | Forloni, Gianluigi

Article Type: Review Article

Abstract: Sirtuins are a family of conserved proteins with deacetylase and ADP-ribosyltransferase activity. In humans they are coded by seven genes (SIRT1-7). The most widely investigated and best known sirtuin is SIRT1, which can be activated by the natural phytocompound resveratrol and plays a role in several physiologic (embryogenesis, glucose metabolism, apoptosis, autophagy, chromatin integrity, and transcriptional state) and pathologic (diabetes, cancer, cardiovascular disorders, and neurodegeneration) conditions. In the field of neurodegeneration, resveratrol and SIRT1 have proved beneficial in in vitro and in vivo models of Alzheimer's disease (AD), reducing amyloid-β protein accumulation, considered one of the pathogenic mechanisms. In contrast …to these promising biological data, however, genetic studies linking SIRT1 variability to AD are negative (this is the case for other sirtuins too, e.g., SIRT3). In this review, we summarize the in vitro, in vivo, and genetic experimental results linking SIRT1 and the other sirtuins to AD, while a description of sirtuins' biochemical features and modulating compounds, as well as sirtuins' involvement in other neurodegenerative disorders are discussed as collateral aims. Show more

Keywords: Alzheimer's disease, genetics, neurodegeneration, resveratrol, review, SIRT1, Sirtuin

DOI: 10.3233/JAD-2010-1215

Citation: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 11-26, 2010

Authors: Polito, Letizia | Chierchia, Armando | Tunesi, Marta | Bouybayoune, Ihssane | Kehoe, Patrick Gavin | Albani, Diego | Forloni, Gianluigi

Article Type: Research Article

Abstract: Environmental enrichment (EE) is a non-pharmacological intervention reported to counteract pathological signs in models of Alzheimer's disease (AD). We developed EE protocols in APP23 mice and evaluated how they influenced cognitive decline and brain amyloid-β (Aβ) burden. We also investigated the involvement of sirtuins (SIRTs) as a possible molecular mediator of EE, by assessing hippocampal and cortical mRNA and protein levels of the SIRT family members (SIRT1 to SIRT7). APP23 transgenic mice were moved to EE cages (TG-EEs) starting from 3 months of age. TG-EEs were compared to transgenic mice housed in standard cages (TG-SHs) and to wild-type littermates in …the two housing conditions (WT-EEs and WT-SHs). At 7 months of age, all mice were tested for behavioral performance with Morris Water Maze (MWM) and visual novel Object Recognition Test (vORT). After a month, a group underwent biochemical analyses, while another group continued in the EE environment till 18 months of age, when Aβ plaque load was assessed. At 7 months, TG-SHs had impaired behavioral performance in MWM and vORT. In contrast, TG-EE mice had restored behavioral performance. At 8 months, EE did not affect AβPP expression or processing, Aβ40/42 , pGlu-Aβ3-40 /3-42 , or Aβ oligomer level. The expression of two Aβ degrading enzymes (insulin degrading enzyme and neprilysin) was not modulated by EE. Brain sirtuin mRNA and protein levels were unchanged, while brain-derived neurotrophic factor expression increased after EE. Aβ deposition was attenuated in 18-month-old TG-EE mice, without apparent reduction of neuroinflammatory signs. We suggest that EE had a beneficial effect on cognitive performance and lessened long-term Aβ accumulation, but brain sirtuin expression was not modulated when cognitive impairment was restored. Show more

Keywords: Alzheimer's disease, APP23 mice, cognitive impairment, environmental enrichment, sirtuin

DOI: 10.3233/JAD-131430

Citation: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 851-864, 2014

Authors: Politis, Antonis | Olgiati, Paolo | Malitas, Petros | Albani, Diego | Signorini, Alessandra | Polito, Letizia | De Mauro, Stefania | Zisaki, Aikaterini | Piperi, Christina | Stamouli, Evangelia | Mailis, Antonis | Batelli, Sara | Forloni, Gianluigi | De Ronchi, Diana | Kalofoutis, Anastasios | Liappas, Ioannis | Serretti, Alessandro

Article Type: Research Article

Abstract: Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-α; IL-6; IFN-γ) and low plasma levels of cyanocobalamin (vitamin B12). Our goal was to relate B12 levels to AD symptoms and to expression of pro-inflammatory cytokines. Clinical manifestations were investigated for a case series of fifty-five outpatients using the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). Plasma B12 levels were measured by radioligand binding assay. Basal and PMA-stimulated levels of IFN-γ, TNF-α, and IL-6 were measured by ELISPOT (PBMC culture supernatant). 47 patients were genotyped for APOE. Ten …patients (18%) had their B12 levels below <250 pg/ml. They did not statistically differ from those 45 who had normal levels in most demographic and clinical features; their MMSE scores were lower (14.7 vs 19.6 p = 0.03) but not after adjustment for disease duration. A greater basal production of IL-6 was reported in patients who had low B12 levels compared to normal B12 subjects (1333 pg/ml vs 976 p < 0.01); this association was confirmed after controlling for age of onset and APOE genotype. In conclusion, low B12 level is associated with greater production of IL-6 in peripheral blood mononuclear cells. Further research is warranted to elucidate whether this neuroinflammatory effect of cobalamin is implicated in the pathophysiology of AD. Show more

Keywords: Alzheimer's disease, APOE gene, cytokine, inflammatory response, vitamin B12

DOI: 10.3233/JAD-2010-1252

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 481-488, 2010

Authors: Serretti, Alessandro | Olgiati, Paolo | Politis, Antonis | Malitas, Petros | Albani, Diego | Dusi, Sabrina | Polito, Letizia | De Mauro, Stefania | Zisaki, Aikaterini | Piperi, Christina | Liappas, Ioannis | Stamouli, Evangelia | Mailis, Antonis | Atti, Anna Rita | Morri, Monica | Ujkaj, Manjola | Batelli, Sara | Forloni, Gianluigi | Soldatos, Costantine R. | Papadimitriou, George N. | De Ronchi, Diana | Kalofoutis, Anastasios

Article Type: Research Article

Abstract: Interleukin-1 (IL1) can contribute to pathophysiology of Alzheimer's disease (AD) by promoting deposition of amyloid-β in the brain. The gene encoding IL1 alpha (IL1A) has a common polymorphism in its 5' regulatory region (rs1800587) with possible functional effects. IL1A T/T genotype has been associated with AD but the overall effect is modest and negative studies have been published. The aim of this study was to investigate the association of the IL1A rs1800587 polymorphism with AD in two independent case-control groups from Greece (Athens) and Italy (Faenza and Granarolo). Preliminary results from the ongoing sample (110 patients with sporadic AD and …130 nonpsychiatric controls) showed no association between IL1A variants and AD, however C/T heterozygotes had more severe depression in AD (Cornell Scale for Depression in Dementia) compared to other genotypes (F = 4.56 , d . f = 1 , p = 0.037 ) after controlling for age, illness duration and cognitive impairment (MMSE). Despite the small sample size and the possibility of a false negative finding, our preliminary data support the hypothesis the IL1A rs1800587 variants are not associated with AD. The effect of the IL1A on depressive symptomatology warrants further investigations, however the lack of a gene-dose relationship would suggest a false positive. Show more

Keywords: Alzheimer's disease, IL-1A gene, inflammatory cytokines, psychosis

DOI: 10.3233/JAD-2009-0946

Citation: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 181-187, 2009