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  • A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis
    Giorgia Zadra, Cornelia Photopoulos, Svitlana Tyekucheva, Pedram Heidari, Qing Ping Weng, Giuseppe Fedele, Hong Liu, Natalia Scaglia, Carmen Priolo, Ewa Sicinska, Umar Mahmood, Sabina Signoretti, Neal Birnberg, Massimo Loda
  • Evolving targets for lipid‐modifying therapy
    1. Rose Q Do1,,
    2. Stephen J Nicholls2 and
    3. Gregory G Schwartz*,1,
    1. 1VA Medical Center, University of Colorado School of Medicine, Denver, CO, USA
    2. 2South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, SA, Australia
    1. *Corresponding author. Tel: +1 303 393 2826; Fax: +1 303 393 5054; E‐mail: Gregory.Schwartz{at}va.gov
    1. This article has been contributed to by US Government employees and their work is in the public domain in the USA

    This review article summarizes existing and emerging therapeutic strategies to modify all types of lipoproteins, whose concentration and function are critical in the progression of atherosclerosis.

    • atherosclerosis
    • cholesterol
    • lipoproteins
    • triglycerides
    • Received April 28, 2014.
    • Revision received June 26, 2014.
    • Accepted July 23, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Rose Q Do, Stephen J Nicholls, Gregory G Schwartz
  • The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT‐TCF pathway responses in human cancer
    1. Alice Melotti1,,
    2. Christophe Mas1,,
    3. Monika Kuciak1,,
    4. Aiala Lorente‐Trigos1,
    5. Isabel Borges1 and
    6. Ariel Ruiz i Altaba*,1
    1. 1Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
    1. *Corresponding author. Tel: +41 22 379 5646; E‐mail: Ariel.RuizAltaba{at}unige.ch
    1. Equal first authorship

    A repositioning screen of clinically approved compounds for WNT‐TCF blockers reveals selective activity in the anti‐parasitic Avermectin macrocyclic lactone family.

    Synopsis

    A repositioning screen of clinically approved compounds for WNT‐TCF blockers reveals selective activity in the anti‐parasitic Avermectin macrocyclic lactone family.

    • The EMEA‐ and FDA‐approved drug Ivermectin is an active WNT‐TCF response blocker in human cancer, mimicking dominant‐negative TCF. Ivermectin blocks human cancer xenograft growth.

    • Initial exploration of Avermectin single molecule derivatives shows that Selamectin is 10 times more potent than Ivermectin, suggesting its clinical testing.

    • Ivermectin and Selamectin show selective anti‐WNT‐TCF activities at low concentrations and these are rescued by direct activation of TCF.

    • Ivermectin is a widely used anti‐parasitic drug with a great safety profile suggesting its additional use to treat WNT‐TCF‐dependent diseases, notably including multiple cancers.

    • cancer
    • Ivermectin
    • TCF
    • WNT
    • xenograft
    • Received March 18, 2014.
    • Revision received July 14, 2014.
    • Accepted July 15, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Alice Melotti, Christophe Mas, Monika Kuciak, Aiala Lorente‐Trigos, Isabel Borges, Ariel Ruiz i Altaba
  • Insulin‐like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice
    1. Maria Pascual‐Lucas1,
    2. Silvia Viana da Silva2,
    3. Marianna Di Scala3,
    4. Carolina Garcia‐Barroso1,
    5. Gloria González‐Aseguinolaza3,
    6. Christophe Mulle2,
    7. Cristina M Alberini4,
    8. Mar Cuadrado‐Tejedor1,5 and
    9. Ana Garcia‐Osta*,1
    1. 1Neurosciences Division, Center for Applied Medical Research, CIMA University of Navarra, Pamplona, Spain
    2. 2Interdisciplinary Institute for Neuroscience, Université of Bordeaux CNRS UMR 5297, Bordeaux, France
    3. 3Gene Therapy and Hepatology Division, Center for Applied Medical Research CIMA University of Navarra, Pamplona, Spain
    4. 4Center for Neural Science, New York University, New York, NY, USA
    5. 5Department of Anatomy, School of Medicine University of Navarra, Pamplona, Spain
    1. *Corresponding author. Tel: +1 34 948 19 47 00 (2023); Fax: +1 34 948 19 47 15; E‐mail: agosta{at}unav.es

    An important role for hippocampal insulin‐like growth factor II (IGF2) was reported for brain plasticity, learning and memory. This study exploits this finding by reporting the role of IGF2 in the pathogenesis of Alzheimer´s disease and suggests a possible strategy for therapeutic use.

    Synopsis

    An important role for hippocampal insulin‐like growth factor II (IGF2) was reported for brain plasticity, learning and memory. This study exploits this finding by reporting the role of IGF2 in the pathogenesis of Alzheimer´s disease and suggests a possible strategy for therapeutic use.

    • Hippocampal IGF2 levels are decreased with aging and in pathological conditions related to AD.

    • IGF2 overexpression in the hippocampus of aged mice enhances memory and prevents dendritic spine loss in CA1 hippocampal neurons.

    • IGF2 overexpression in the hippocampus of AD mice reverse memory and synaptic deficits and prevents dendritic spine loss in CA1 hippocampal neurons.

    • IGF2 receptor is involved in the extracellular Aβ degradation and suggests that IGF2R may be involved in the Aβ clearance observed in IGF2‐treated Tg2576 mice.

    • Alzheimer's disease
    • IGF1
    • IGF2
    • IGF2R
    • synaptic plasticity
    • Received May 7, 2014.
    • Revision received July 11, 2014.
    • Accepted July 16, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Maria Pascual‐Lucas, Silvia Viana da Silva, Marianna Di Scala, Carolina Garcia‐Barroso, Gloria González‐Aseguinolaza, Christophe Mulle, Cristina M Alberini, Mar Cuadrado‐Tejedor, Ana Garcia‐Osta