Page 121 - CIBERER-2015-eng

Most relevant scientific articles
Research Groups
raththagala m, BreWer K.m., ParKer m.W., sherWood a.r., Wong B.K., hsu s., Bridges t.m., Paasch B.c, hell- man l.m, husodo s., meeKins d.a., taYlor a.o., turner B.d., auger K.d., duKhande V.V., chaKraVarthY s., sanZ P., Woods V.V., li s., Vander Kooi c.W. and gentrY m.s. “Structural Mechanism of Laforin Function in Glycogen Dephosphorylation and Lafora Disease”. Molecular Cell. 2015, 57: 261-272.
romá-mateo, c., aguado, c., garcía-giméneZ, J.l.,
Berthier, a., PaYá, m., garcía-caBrero, a.m., Ballester, m.i., heredia, m., serratosa, J.m., sáncheZ, m.P., sanZ, P. “Pharmacológical interventions to ameliorate neuro- pathológical symptoms in a mouse model of Lafora dis- ease”. Mol. Neurobiol, 2015, PMID: 25627694.
Romá-Mateo, C., Aguado, C., García-Giménez, J.L., Knecht, E., Sanz, P., Pallardó, F.V. “Oxidative stress, a new hallmark in the pathophysiology of Lafora progressive myoclonus epilepsy”. Free Rad. Biol. Med. 2015, 88: 30-41.
iBañeZ-caBellos, s., seco-cerVera, m. Pallardo, F.V., Knecht, e., sanZ, P. “Increased oxidative stress and im- pairment of antioxidant systems in Lafora disease mod- els”. Mol. Neurobiol. 2015, 51: 932-946.
Highlights
During 2015 we have contributed to the understand- ing of the pathophysiological basis of Lafora dis- ease. First, we have collaborated in the description of the molecular structure of the protein phosphatase laforin. These results will allow the understanding of the pathological defects of the mutations in the cor- responding gene found in Lafora disease patients and in the design of personalized medicine. We have also described that Lafora disease is characterized by the presence of conditions of oxidative stress that are produced by a mitochondrial dysfunction. Finally, we have described that the treatment of murine models of disease with 4-phenylbutirate (a chemical chaperone) and metformin (an activator of protein kinase AMPK) decreases the accumula- tion of Lafora bodies in the brain of treated animals, diminishes neurodegeneration and alleviates the neuropathological symptoms of the disease. These results open the possibility for establishing a clini- cal trial in human patients, since these compounds
sáncheZ-martin, P., romá-mateo, c., Viana, r. and sanZ, P. “Ubiquitin conjugating enzyme E2-N and sequestosome 1 (p62) are components of the ubiquitination process me- diated by the malin-laforin E3-ubiquitin ligase complex”. Int. J. Biochem Cell Biol 2015, 69: 204-214.
have good safety records and are currently being used in the treatment of other pathologies. These results appeared published in the outstanding news of the CIBERER web page in May and June 2015.
The group has been co-author of two patents in 2015 (PCT/ES2015/070677 y P201531786) on new activators of protein kinase AMPK and its use in the treatment of diabetes and related diseases. One of them was chosen to be presented in the FarmaIn- dustria meeting in November 2015 to check the in- terest of the Pharma companies that participated in the event.
Finally, the group has participated in the organiza- tion of information events on rare diseases, such as the VII Meeting “Investigar es Avanzar” (Rare diseas- es world day, Valencia 25th February) and the “Aso- ciación Valenciana de Enfermedad de Huntington, AVAEH” (Valencia, 21st November 2015).
Institution: Agencia Estatal Consejo Superior de Investigaciones Científicas
Contact: Institituto de Biomedicina de Valencia · Jaume Roig, 11. 46010 Valencia · Tel.: 96 339 17 60
CIBERER I Annual report 2015 I 121