on Cell reports
by Lassot I, Mora S, Lesage S, Zieba BA, Coque E, Condroyer C, Bossowski JP, Mojsa B, Marelli C, Soulet C, Tesson C, Carballo-Carbajal I, Laguna A, Mangone G, Vila M, Brice A, Desagher S
Although accumulating data indicate that increased α-synuclein expression is crucial for Parkinson disease (PD), mechanisms regulating the transcription of its gene, SNCA, are largely unknown. Here, we describe a pathway regulating α-synuclein expression. Our data show that ZSCAN21 stimulates SNCA transcription in neuronal cells and that TRIM41 is an E3 ubiquitin ligase for ZSCAN21. In contrast, TRIM17 decreases the TRIM41-mediated degradation of ZSCAN21. Silencing of ZSCAN21 and TRIM17 consistently reduces SNCA expression, whereas TRIM41 knockdown increases it. The mRNA levels of TRIM17, ZSCAN21, and SNCA are simultaneously increased in the midbrains of mice following MPTP treatment. In addition, rare genetic variants in ZSCAN21, TRIM17, and TRIM41 genes occur in patients with familial forms of PD. Expression of variants in ZSCAN21 and TRIM41 genes results in the stabilization of the ZSCAN21 protein. Our data thus suggest that deregulation of the TRIM17/TRIM41/ZSCAN21 pathway may be involved in the pathogenesis of PD.
on Movement disorders : official journal of the Movement Disorder Society
by Cormier-Dequaire F, Bekadar S, Anheim M, Lebbah S, Pelissolo A, Krack P, Lacomblez L, Lhommée E, Castrioto A, Azulay JP, Defebvre L, Kreisler A, Durif F, Marques-Raquel A, Brefel-Courbon C, Grabli D, Roze E, Llorca PM, Ory-Magne F, Benatru I, Ansquer S, Maltête D, Tir M, Krystkowiak P, Tranchant C, Lagha-Boukbiza O, Lebrun-Vignes B, Mangone G, Vidailhet M, Charbonnier-Beaupel F, Rascol O, Lesage S, Brice A, Tezenas du Montcel S, Corvol JC,
Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD.
on Allergologia et immunopathologia
by Mori F, Angelucci C, Cianferoni A, Barni S, Indolfi G, Casini A, Mangone G, Materassi M, Pucci N, Azzari C, Novembre E
Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations.
on Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases
by Pratelli E, Alito A, Zanella C, Busi L, Mangone G, Scarselli M, Pasquetti P
Osteoporotic fractures are associated with a significant increase in morbidity, mortality and medical costs. There is also a strong link between fractures and increased mortality. Among effective measures for the prevention of falls, instability treatment surely plays a crucial role. Several factors contribute to instability, many of which are ageing-related: visual spatial deficit, strength reduction, weight imbalance with COP lateralization sometimes favoured by LLD (leg length discrepancy). It seems useful to detect an heterometry which could be corrected, if present. The aim of our work is to assess the responses of individuals with heterometry diagnosis to the wedge positioning, using the balance board Lizard 3.0®. In the period between January 2013 and September 2013, 52 patients were recruited with clinical heterometry >5 mm among those that were treated in the Recovery and Rehabilitation Agency's postural clinic of the Careggi Hospital Orthopedic Trauma Centre in Florence. Our measurements have revealed that there is a statistically significant correlation (p<0.5) between clinical limb shortening expressed in mm and location of the weight imbalance at the stabilometric examination at T0; our data shows that the majority of patients with clinical heterometry shows a weight imbalance on the longer limb. After heterometry correction, 21 patients showed a statistically significant reduction (p<0,01) in weight imbalance expressed in kg between T0 and T1 and have been assigned to group 1, the remaining 31 worsened and have been assigned to group 2. From the results of our study, it is clear that the correction of lower limbs heterometry shouldn't be based only on clinical measuring of the limbs length discrepancy, even if very accurate.
on Movement disorders : official journal of the Movement Disorder Society
by Lee AJ, Wang Y, Alcalay RN, Mejia-Santana H, Saunders-Pullman R, Bressman S, Corvol JC, Brice A, Lesage S, Mangone G, Tolosa E, Pont-Sunyer C, Vilas D, Schüle B, Kausar F, Foroud T, Berg D, Brockmann K, Goldwurm S, Siri C, Asselta R, Ruiz-Martinez J, Mondragón E, Marras C, Ghate T, Giladi N, Mirelman A, Marder K,
Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80.
on Italian journal of pediatrics
by Barni S, Mori F, Valleriani C, Mangone G, Testi S, Saretta F, Sarti L, Pucci N, de Martino M, Azzari C, Novembre E
The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults.
on Neurobiology of aging
by Giri A, Mok KY, Jansen I, Sharma M, Tesson C, Mangone G, Lesage S, Bras JM, Shulman JM, Sheerin UM, , Díez-Fairen M, Pastor P, Martí MJ, Ezquerra M, Tolosa E, Correia-Guedes L, Ferreira J, Amin N, van Duijn CM, van Rooij J, Uitterlinden AG, Kraaij R, Nalls M, Simón-Sánchez J
Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.
on Lancet (London, England)
by Indolfi G, Mangone G, Bartolini E, Moriondo M, Azzari C, Resti M
on The Journal of steroid biochemistry and molecular biology
by Orefice N, Carotenuto A, Mangone G, Bues B, Rehm R, Cerillo I, Saccà F, Calignano A, Orefice G
Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses.
on Human vaccines & immunotherapeutics
by Azzari C, Cortimiglia M, Nieddu F, Moriondo M, Indolfi G, Mattei R, Zuliani M, Adriani B, Degl'Innocenti R, Consales G, Aquilini D, Bini G, Di Natale ME, Canessa C, Ricci S, de Vitis E, Mangone G, Bechini A, Bonanni P, Pasinato A, Resti M
The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.