Early defect of transforming growth factor β1 formation in Huntington's disease.

A defective expression or activity of neurotrophic factors, such as brain- and glial-derived neurotrophic factors, contributes to neuronal damage in Huntington's disease (HD). Here, we focused on transforming growth factor-beta (TGF-beta(1)), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF-beta(1) levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post-mortem brain tissues showed that TGF-beta(1) was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF-beta(1) in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF-beta(1) formation in asymptomatic R6/2 mice, where blood TGF-beta(1) levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF-beta(1) formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF-beta(1) production is associated with HD. Accordingly, reduced TGF-beta(1) mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock-in cell lines expressing full-length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF-beta(1) levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF-beta(1) levels in the brain may influence the progression of HD

La Bibbia nella letteratura italiana. Antico Testamento

Questo volume tematico sui rapporti tra Antico Testamento e Letteratura italiana vuole essere una prima organica, anche se non sistematica mappatura di temi, storie e personaggi della nostra tradizione letteraria, non aliena da alcune incursioni in ambito europeo. Nel volume trovano sede saggi su eventi (la Creazione degli animali, l\u2019Esodo e la Terra promessa, la torre di Babele); fl agelli e punizioni (il Diluvio e l\u2019Arca di No\ue8); personaggi (Adamo, Caino e Abele, Isacco, Giobbe, Susanna, Giona, Qo\ue8let); ma anche fi gure bibliche complesse e controverse come Satana, che permangono lungo i tempi della storia (dall\u2019et\ue0 medievale a quella romantica); luoghi (il Paradiso terrestre); interpretazioni dei sogni biblici secondo una lettura onirocritica e un saggio dedicato alle tangenze tra Cantico dei Cantici e poesia italiana. Completa il volume un\u2019analisi delle riscritture veterotestamentarie nella letteratura giudaico-italiana di et\ue0 moderna e contemporanea