Neural stem cell derived neurons obtained from human pluripotent stem cells as an in vitro model for studying CDK5/p35 mediated neurodegenerative processes

MUCCI, SOFÍA; RODRÍGUEZ VARELA, MARÍA SOLEDAD; ISAJA, LUCIANA; SEVLEVER, GUSTAVO EMILIO; SCASSA, MARÍA ELIDA; ROMORINI, LEONARDO

Mar del Plata

Congreso; LXIII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

SAIC

Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) can differentiate into a wide range of specialized cells, including neural stem cells (NSC). Moreover, NSC-derivedneurons are proposed as a model for studying neurodegeneration. CDK5/p35 complex is involved in neuronal homeostasis and development, as axon guidance, dendrites development and functional synapses. However, its function is deregulated inneurodegeneration by p35 cleavage into p25 by calpains, which allows the aberrant phosphorylation of targets through the constitution of a more stable complex CDK5/p25 and itstranslocation to the nucleus. There are different stressors, like Rotenone, that induce a CDK5/p25 based neurodegenerative stress in primary neuronal cultures and animal models. In this work we aimed to set up an in vitro CDK5/p25 neurodegenerative model using NSC-derived neurons obtained from hESCs (H9 line) and hiPSCs (FN2.1 line) obtained in ourlaboratory, subjected to different cellular stressors such as Rotenone, A23187 calcium ionophore and glutamate.