In vitro treatments with ceftriaxone promote elimination of mutant glial fibrillary acidic protein and transcription down-regulation.

[alexander disease]

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 alphaB-Crystallin , HSP 27 , ubiquitin and proteasome components . Recent findings indicate that up-regulation of alphaB-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 HSP 27 and alphaB-Crystallin , polyubiquitination and autophagy . Ceftriaxone has also been shown to modulate the proteasome system , thus decreasing NF-kappaB 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 .

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Diseases presenting "other neurodegenerative disorders" symptom

alexander disease

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