Huntington＇s disease （HD） is the most common dominantly inherited neurodegenerative disorder, mainly characterized by the progressive striatal and cortical neurodegeneration and as- sociated motor, cognitive and be...Huntington＇s disease （HD） is the most common dominantly inherited neurodegenerative disorder, mainly characterized by the progressive striatal and cortical neurodegeneration and as- sociated motor, cognitive and behavioural disturbances （Zuccato et al., 2010）. The disease-causing mutation is an expansion of a GAG trinucleotide repeat （〉 36 repeats） encoding a polygluta- mine stretch in the N-terminal region ofhuntingtin （Htt） （Zuc- cato et al., 2010）, a ubiquitous protein whose function is still unclear （Zuccato et al., 2010）. Expansion of the polyQ stretch endows mutant Htt （mHtt） with toxic properties, and results in the development of a broad array of undesirable effects in both neuronal and non-neuronal cells （Zuccato et al., 2010）. Among all cellular dysfunctions and biochemical imbalances classically associated with HD, perturbed metabolism of （glyco） sphingolipids appears to play a crucial role in the pathogenesis of the disease. Over the last years, we and other have extensively contributed to these findings （Desplats et al., 2007;展开更多
基金supported by"Fondazione Neuromed"funded by Italian Ministry of Health"Ricerca Corrente"funding program
文摘Huntington＇s disease （HD） is the most common dominantly inherited neurodegenerative disorder, mainly characterized by the progressive striatal and cortical neurodegeneration and as- sociated motor, cognitive and behavioural disturbances （Zuccato et al., 2010）. The disease-causing mutation is an expansion of a GAG trinucleotide repeat （〉 36 repeats） encoding a polygluta- mine stretch in the N-terminal region ofhuntingtin （Htt） （Zuc- cato et al., 2010）, a ubiquitous protein whose function is still unclear （Zuccato et al., 2010）. Expansion of the polyQ stretch endows mutant Htt （mHtt） with toxic properties, and results in the development of a broad array of undesirable effects in both neuronal and non-neuronal cells （Zuccato et al., 2010）. Among all cellular dysfunctions and biochemical imbalances classically associated with HD, perturbed metabolism of （glyco） sphingolipids appears to play a crucial role in the pathogenesis of the disease. Over the last years, we and other have extensively contributed to these findings （Desplats et al., 2007;
