Page 151 - CIBERER-2015-eng

Most relevant scientific articles
Research Groups
morató l, ruiZ m, Boada J, calingasan nY, galino J, guilera c et al. Redox regulation of SIRT1 controls mito- chondrial function and underlies axonal degeneration. Cell Death Differ. 2015; 22:1742-1753.
launaY n, aguado c, Fourcade s, ruiZ m, grau l, riera J et al. Autophagy induction halts axonal degeneration in a mouse model of X-adrenoleukodystrophy. Acta Neuro- pathol. 2015; 129:399-415.
ruiZ m, JoVe m, schluter a, casasnoVas c, VillarroYa F, guilera c et al. Altered glycolipid and glycerophospho- lipid signaling drive inflammatory cascades in adrenomy- eloneuropathy. Hum Mol Genet. 2015; 24(24):6861-76.
Highlights
In 2015 we achieved to:
i) increase the knowledge of molecular basis and pathophysiology in X-ALD;
ii) identify new therapeutic targets as the mitochon- drial biogenesis drivers (Sirt1/PGC-1/PPARy axis) and autophagic flux (via mTOR);
iii) demonstrate, through integrated analysis sys- tems, that the AMN patients also exhibit altera- tions in pro-inflammatory cascades;
and iv) identify drugs like resveratrol or temsiroli- mus, able to reverse the axonal degeneration in the mouse model.
We also finished the first year of treatment of AMN patients included in a multicenter international phase II clinical trial with biotin and started a new phase II clinical trial with pioglitazone, promoted by our unit. We have also initiated the proceedings to obtain the orphan drug designation for temsirolimus in ALD (with U721).
Fourcade s, Ferrer i, and PuJol a. Oxidative stress, mi- tochondrial and proteostasis malfunction in adrenoleu- kodystrophy: A paradigm for axonal degeneration. Free Radic Biol Med. 2015; 88(Pt A):18-29.
KrusKa n, schönFeld P, PuJol a and reiser g. Astro- cytes and mitochondria from adrenoleukodystrophy protein (ABCD1)-deficient mice reveal that the adrenoleu- kodystrophy-associated very long-chain fatty acids target several cellular energy-dependent functions. Biochim Bio- phys Acta. 2015; May;1852(5):925-36.
Within the PDI structure, we started the intramu- ral project achieved in the ACCI 2014 call, together with U703 and U711 units for the identification and functional and metabolic characterization of new variants/genes involved in leukodystrophies and spastic paraplegia. We have already identified some new variants, being currently validated in the zebraf- ish model.
At international level, we started in 2013 to collab- orate with Dr. G. Reiser from Magdeburg, Germa- ny, with a first publication in Biochim Biophys Acta in 2015. In addition, we have been included in the MSeqDR Consortium, which aims to facilitate depo- sition, curation, annotation, and integrated systems biology approach analysis of genomic data for the mitochondrial disease clinical and research com- munities.
Finally, as members of the SEFALer platform, we continue to perform phenotyping services of loco- motor disorders and neuromuscular coordination for the interested groups.
Institution: Fundación IDIBELL · Contact: Hospital Duran i Reynals · Gran Vía, s/n, km. 2,7 08907 Hospitalet de Llobregat · Tel.: 93 260 71 37 · E.mail: [email protected]
Website: http://www.neurometabolic-lab.org/
CIBERER I Annual report 2015 I 151