Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a CAG trinucleotide repeat in the Huntingtin gene (Htt), which results in translation of a protein containing an enlarged CAG- encoded polyglutamine (polyQ) characterized by the progressive degeneration of neurons in the brain during aging. This results in chorea (involuntary movement), death. The glutamate-glutamine cycle is fundamental in maintaining neuronal function and survival. When glutamate homeostasis levels in neurons increase, resulting in neuronal death. Glial cells also have an important function in maintaining this homeostasis, removal from the synaptic cleft by glial cells is reduced in a mouse HD model suggesting that glia actively participate in the HD. But how does the glutamate-glutamine cycle contribute to neuronal death? And how does signaling in glial cells contribute pathogenesis in HD? To answer these questions we are using a Drosophila model that has been successfully used to dissect the events in polyQ-related diseases including HD. Our preliminary data show that manipulation of components of the glutamine-neuronal death and ameliorate the motility of animals expressing the HttQ93 in neurons using ELAV. Activation of TOR signaling functions in neurons as a cleaning/survival mechanism. We would like to understand how components of the TOR pathway act glutamate-glutamine cycle, and what controls autophagy in neuronal cells. With this approach we hope to provide novel insights that cause neuronal degeneration not only in Huntington's diseases but also in other neuronal pathologies related to the aging work was sponsored by the Ministero degli Affari Esteri e Cooperazione Internazionale.
|Titolo:||The role of the glutamine-glutamate cycle in neuronal degeneration induced by the mutant human Huntington PolyQ protein|
PASINI, MARIA ENRICA (Primo)
|Data di pubblicazione:||2015|
|Settore Scientifico Disciplinare:||Settore BIO/06 - Anatomia Comparata e Citologia|
|Citazione:||The role of the glutamine-glutamate cycle in neuronal degeneration induced by the mutant human Huntington PolyQ protein / M.E. Pasini, M. Raneli, L. Vernizzi, N..T. Tue, P. Bellosta. ((Intervento presentato al 56. convegno Annual Drosophila Research Conference tenutosi a Chicago nel 2015.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|