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Most relevant • launay n, ruiz M, Fourcade s, schlüter a, Guilera c, Ferrer i, knecht e, PuJol a (2013).
Oxidative stress regulates the ubiquitin-proteasome system and immunoproteaso-
scientific
me functioning in a mouse model of X-adrenoleukodystrophy. Brain 136, 891-904.
articles
• Vidal-donet JM, cárcel-trullols J, casanoVa b, aGuado c, knecht e (2013). Alterations
in ROS activity and lysosomal pH account for distinct patterns of macroautophagy

in LINCL and JNCL fibroblasts. PLoS One 8(2):e55526.

• Moruno-Manchón JF, Pérez-JiMénez e, knecht e (2013). Glucose induces autophagy
under starvation conditions by a p38 MAPK-dependent pathway. Biochem. J. 449,

497-506.

• García-GiMénez Jl, seco-cerVera M, aGuado c, roMá-Mateo c, dasí F, PrieGo s, MarkoVic

J, knecht e, sanz P, Pallardó FV (2013). Lafora disease fibroblasts exemplify the mo-
lecular interdependence between thioredoxin 1 and the proteasome in mammalian
ó
cells. Free Radic. Biol. Med. 65, 347-359.

• erraFiy r, aGuado c, Ghislat G, esteVe JM, Gil a, loutFi M, knecht e (2013). PTEN in-
creases autophagy and inhibits the ubiquitin-proteasome pathway in glioma cells

Independently of its lipid phosphatase activity. PLoS One 8(12):e83318.

Our laboratory, in addition to CIBER, is funded by the following agencies: “Mara-
Highlights
t” from TV3 (Ref. 110131), MINECO (Ref. BFU2011-22630) and the “Prometeo”

program for excellence groups of the Valencian Community (Ref. 2012/ 061).
We investigate the implications of alterations in intracellular protein degradation

pathways and their regulation in rare diseases, including:

• Neuronal ceroid lipofuscinosis (NCL): Besides similarities, we have found
differences between fibroblasts from patients with late infantile (LINCL/CLN2)

and juvenile (JNCL/CLN3) NCL, which may explain the earlier onset of symptoms

in the first. In CLN2 there is a greater accumulation of ROS produced by a loss
in the activity of the TPP1 enzyme, whereas in CLN3 this loss is only partial and

due to an increased lysosomal pH.

• Lafora disease: In collaboration with six other CIBER laboratories we are

integrated in the Lafora Consortium that coordinately investigates this pathology.
The most relevant aspects we have found in 2013 in all models of this disease

are: i) a defective formation of autophagosomes, and ii) an increase in oxidative é

stress caused by defects in autophagy and in the antioxidant defence system,
mainly in the mitochondrial isoform of superoxide dismutase and in catalase.

• X-Adrenoleukodystrophy: In collaboration with the 759U, we have found that

autophagic flux is impaired and that this depends on mTOR activation.

• Retinitis pigmentosa (RP): In collaboration with the 718U we have shown that

CERKL (Ceramide Kinase-Like), one of the proteins mutated in RP, is a component
of compact and untranslated mRNPs, as well as of other RNPs complexes (stress 13
20
granules, “P- bodies” and polysomes). CERKL interacts with different proteins T
OR
such as eIF3B, PABP, HSP70 and RPS3, and binds to mRNAs through its amino- P
terminal part.
RE
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In addition, three PhD theses have been defended this year and have been awar- A
NU
ded with “summa cum laude” (Ghita Ghislat, Flix Moruno and Rajaa Errafiy).
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