Glial cells play key roles in developmental and neurodegenerative disorders, including some with remarkable similarities with ARSACS, such as Alexander disease and Giant Axonal Neuropathy. We and others have found high levels of sacsin expression in rodent and human astroglia and microglia. Sacsin deletion in rat astroglial-like cells disrupts glial intermediate filament networks (GFAP, Vimentin, Nestin) and the response of these cells to oxidative stress and inflammatory cues. These results indicated that sacsin is relevant for glial biology and opened the possibility that alterations in glial cells could be involved in ARSACS. To address these issues, we will 1) develop new ARSACS astroglial and microglial human cell models and analyze their molecular and cellular alterations (Herrera Lab); and 2) analyze glial behavior and function during neuronal development and disease manifestation in mouse (Fernandes Lab) and zebrafish (Adams Lab) models of ARSACS. If we find relevant glial alterations during this descriptive approach, we intend to advance towards the design and preclinical testing of potential therapeutic interventions. Our results could lay the groundwork for formulating new therapeutic strategies targeting glia rather than neurons in ARSACS and similar pathologies.

Grant: $100,000

Duration: one year


Dr. Federico Herrera, Dep. of Chemistry and Biochemistry (DQB)
 Faculty of Sciences, University of Lisbon
 Edifício C8, Campo Grande, 1749-016 Lisboa

Dr. Adelaide Fernandes

Dep. of Pharmaceutical Sciences and Medicines Faculty of Pharmacy, University of Lisbon
Avenida, Professor Gama Pinto,1649-003 Lisboa

        Dr. Michelle Adams

         Psychology department, Bilkent University

         Ankara, TR 06800