<i>In vitro</i> treatments with ceftriaxone promote elimination of mutant glial fibrillary acidic protein and transcription down-regulation

Alexander disease is a rare, untreatable and usually fatal neurodegenerative disorder caused by heterozygous mutations of the glial fibrillary acidic protein (GFAP) gene which ultimately lead to formation of aggregates, containing also αB-Crystallin, HSP27, ubiquitin and proteasome components. Recent findings indicate that up-regulation of αB-Crystallin in mice carrying GFAP mutations may temper the pathogenesis of the disease. Neuroprotective effects of ceftriaxone have been reported in various animal models and, noteworthy, we have recently shown that the chronic use of ceftriaxone in a patient affected by an adult form of Alexander disease could halt its progression and ameliorate some of the symptoms. Here we show that ceftriaxone is able to reduce the intracytoplasmic aggregates of mutant GFAP in a cellular model of Alexander disease. Underlying mechanisms include mutant GFAP elimination, concurrent with up-regulation of HSP27 and αB-Crystallin, polyubiquitination and autophagy. Ceftriaxone has also been shown to modulate the proteasome system, thus decreasing NF-κB activation and GFAP promoter transcriptional regulation, which further accounts for the down-modulation of GFAP protein levels. These mechanisms provide previously unknown neuroprotective targets of ceftriaxone and confirm its potential therapeutic role in patients with Alexander disease and other neurodegenerative disorders with astrocyte involvement

Anatomia umana. Cofanetto. Basato sul Prometheus

L'opera, basata sul Prometheus di M. Schünke, E. Schulte e U. Schumacher con illustrazioni di M. Voll e K. Wesker, include tre volumi: I, Basi Anatomiche per la Semeiotica; II, Basi Anatomiche per la Fisiopatologia; III: Basi Anatomiche per le Neuroscienze. Il trattato è impostato in maniera moderna, rendendo complementari la trattazione regionalistica e quella sistematica, prevedendone e consentendone il pieno utilizzo virtualmente in tutte le sedi accademiche, a prescindere dal numero di crediti e dall’organizzazione del corso. Ne risulta uno strumento didattico che consentirà non solo la personalizzazione dello studio, ma anche il successivo approfondimento dei contenuti per tutta la vita professionale del medico