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Targeting the dream protein: new avenues for the search of drugs for neurodegenerative diseases

AuthorsCercós, Pilar ; García-López, M. Teresa ; Herranz, Rosario ; Martín-Martínez, Mercedes ; Prieto, Ángela ; Valenzuela, Carmen ; Naranjo, José Ramón; Gutiérrez-Rodríguez, Marta
Issue Date2013
PublisherSociedad Española de Química Terapéutica
CitationIII SEQT Summer School (2013)
AbstractAltered neuronal calcium homeostasis and early compensatory changes in transcriptional programs are common features of many neurodegenerative pathologies including Alzheimer’s disease (AD), Down syndrome (DS) and Huntington’s disease (HD). DREAM (Downstream Regulatory Element Antagonist Modulator), also known as calsenilin or KChIP-3 (potasium channel interacting protein-3), is a multifunctional Ca2+ binding protein that controls the expression level and/or the activity of several proteins related to Ca2+ homeostasis, neuronal excitability and neuronal survival. This protein is widely expressed in the brain and, depending on the cell type and physiological conditions, shows multiple subcellular localizations, in the nucleus, cytosol or cell membrane. Initially, the interest in DREAM was based on its key role in the regulation of intracelular Ca2+ levels. An early reduction in DREAM levels is found in the pre-symptomatic phase of several neurodegenerative mouse models, including AD, DS and HD. These data support the idea that an early down regulation of the DREAM level in neurons during the pre-symptomatic phase of the AD, DS and HD might be part of its neuroprotective mechanism. These findings suggest that DREAM could be a novel and versatile target for therapeutic intervention in neurodegeneration and that molecules able to bind to DREAM and block its physiological functions could be candidates of drugs to treat neurodegenerative diseases. Up to know, low molecular weight molecules have not been described able to interact with DREAM and to modulate its action. In this communication we report the rational design, the synthesis and the biological evaluation of novel DREAM-binding molecules.
DescriptionResumen del póster presentado al III SEQT Summer School: "Medicinal Chemistry in Drug Discovery: The Pharma Perspective", celebrado en Tres Cantos (Madrid) del 25 al 27 de junio de 2013.
Appears in Collections:(IIBM) Comunicaciones congresos
(IQM) Comunicaciones congresos
(CNB) Comunicaciones congresos
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