PT  - JOURNAL ARTICLE
AU  - Luisa Vernizzi
AU  - Chiara Paiardi
AU  - Giusimaria Licata
AU  - Teresa Vitali
AU  - Stefania Santarelli
AU  - Martino Raneli
AU  - Vera Manelli
AU  - Manuela Rizzetto
AU  - Mariarosa Gioria
AU  - Maria E. Pasini
AU  - Daniela Grifoni
AU  - Maria A. Vanoni
AU  - Cinzia Gellera
AU  - Franco Taroni
AU  - Paola Bellosta
TI  - Glutamine Synthetase-1 induces autophagy-lysosomal degradation of Huntingtin aggregates and ameliorates animal motility in a <em>Drosophila</em> model for HD
AID  - 10.1101/618629
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 618629
4099  - http://biorxiv.org/content/early/2019/04/26/618629.short
4100  - http://biorxiv.org/content/early/2019/04/26/618629.full
AB  - Glutamine Synthetase1 (GS1) is an enzyme that catalyzes the ATP-dependent synthesis of L-glutamine from L-glutamate and ammonia as a key element of the glutamate glutamine cycle, a complex physiological process occurring between glia and neurons, necessary to control the homeostasis of glutamate. Using a Drosophila model for Huntington’s disease, we report that expression of GS1 in neurons ameliorates the motility defects of animals expressing the mutant Httex1-Q93 form of the gene huntingtin. At the cellular level, expression of GS1 increases the basal level of autophagy and significantly reduces the size of the toxic Htt-Q93 protein aggregates. In addition, we found that expression of GS1 prevents TOR localization at the lysosomal membrane and reduction in the phosphorylation of its effector S6K. This study reveals a novel function for GS1 in neurons linking its activity to the inhibition of TOR signaling and autophagy. The identification of novel pharmacological regulators of autophagy is of particular interest considering its beneficial role in controlling neuronal health and counteracting the detrimental effects of toxic aggregates of proteinopathies including Huntington’s disease.