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Dream-modulators for dreaming of novel drugs for neurodegenerative diseases

AuthorsCercós, Pilar CSIC; Peraza, Diego A.; Prieto, Ángela CSIC; González, Teresa; Mellström, Britt; García-López, M. Teresa CSIC; Herranz, Rosario CSIC ORCID; Martín-Martínez, Mercedes CSIC ORCID; Valenzuela, Carmen CSIC ORCID; Naranjo, José Ramón; Gutiérrez-Rodríguez, Marta CSIC ORCID
Issue Date2015
CitationSIMCC 2015
AbstractAltered neuronal calcium homeostasis and early compensatory changes in transcriptional programs are common features of many neurodegenerative pathologies including Alzheimer's disease, Down syndrome and Huntington's disease. DREAM (Downstream Regulatory Element Antagonist Modulator, also known as calsenilin or KChIP-3 (potassium channel interacting protein-3), is a multifunctional calcium binding protein that controls the expression level and/or the activity of several proteins related to calcium 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. The interest in DREAM is based on its key role in the regulation of intracellular calcium levels. As a calcium-dependent transcriptional repressor, DREAM is a master regulator of activity-dependent gene expression and controls genes important for calcium homeostasis. As an auxiliary protein in the plasma membrane, DREAM interacts with and regulates the gating of Kv4 potassium channels, L- and T-type voltage-dependent calcium channels and NMDA receptors. 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 modulate its physiological functions could be candidates for drugs to treat neurodegenerative diseases. Moreover, up to now, only two DREAMbinding molecules have been identified. In this communication we report the rational design and the synthesis of novel DREAM-binding molecules and their effects on the modulation of DREAM/protein interactions.
DescriptionResumen del póster presentado al Spanish-Italian Medicinal Chemistry Congress, celebrado en Barcelona (España) del 12 al 15 de julio de 2015.
Appears in Collections:(IQM) Comunicaciones congresos
(CNB) Comunicaciones congresos
(IIBM) Comunicaciones congresos
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