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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy causing ventricular tachycardia following adrenergic stimulation. Pathogenic variants in RYR2-encoded ryanodine receptor 2 (RYR2) cause CPVT1 and cluster into domains I-IV, with the most N-terminal domain involving residues 77-466. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated for RYR2-F13L, -L14P, -R15P, and -R176Q variants. Isogenic control iPSCs were generated using CRISPR-Cas9/PiggyBac. Fluo-4 Ca

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg− 1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h after intraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well. Fil: Cukierman, Daphne Schneider. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Pinheiro, Ana Beatriz. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Castiñeiras-Filho, Sergio L.P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Silva, Anastácia Sá P.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: De Falco, Anna. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: de P. Ribeiro, Thales. Universidade Federal do Rio de Janeiro; Brasil Fil: Maisonette, Silvia. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: da Cunha, Alessandra L.M.C.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Hauser-Davis, Rachel A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Aucélio, Ricardo Q.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania Fil: Pereira, Marcos D.. Universidade Federal do Rio de Janeiro; Brasil Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Rey, Nicolás A.. Pontifícia Universidade Católica do Rio de Janeiro; Brasil