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Huntington's disease: Huntingtin roles during cell fate decision

Grant number: 15/13345-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2015
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Alexander Henning Ulrich
Grantee:Talita Glaser
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM
Associated scholarship(s):16/07659-6 - Huntingtin's Roles in Fate Decision of GABAergic Neurons Derived from iPSCs of HD Patients, BE.EP.PD

Abstract

Huntington's disease (HD) is a dominant inherited neurodegenerative disorder that is caused by mutation within the coding region of the huntingtin (HTT) gene, resulting in an elongated stretch of glutamine near the NH2 terminus of the protein. The consequence of HD mutation is a massive brain neurodegeneration characterized by the loss of GABAergic neurons from the basal ganglia. To fulfill the urge of developing treatments for HD, we need to elucidate the molecular mechanisms that control neural stem cell differentiation to GABAergic neurons. Intracellular calcium oscillations can modulate many cell processes like gene transcription, differentiation and even cell death. Spitzer and coworkers have already described in Xenopus laevis that increases in spontaneous Ca2+ spikes frequency favors glutamatergic differentiation, these oscillations depends on IP3 receptor activity, which can be modulated by mHtt. Therefore, in this project we aim to elucidate the role of Htt/mHtt in spontaneous calcium oscillations during differentiation and in cell fate choice due to pro-neural gene expression, by using a cell model (CTE) that resembles the embryo development in vitro. In addition, we will also investigate intracellular signaling pathways by which wild type Htt can control early embryo development, since the knockout is lethal before reaching gastrulation.

Scientific publications (14)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANDREJEW, ROBERTA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE ELISA; GLASER, TALITA; ARNAUD-SAMPAIO, VANESSA FERNANDES; LAMEU, CLAUDIANA; ULRICH, HENNING. The P2X7 Receptor: Central Hub of Brain Diseases. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 13, JUL 31 2020. Web of Science Citations: 0.
ARNAUD-SAMPAIO, VANESSA F.; RABELO, IZADORA L. A.; BENTO, CAROLINA A.; GLASER, TALITA; BEZERRA, JEAN; COUTINHO-SILVA, ROBSON; ULRICH, HENNING; LAMEU, CLAUDIANA. Using Cytometry for Investigation of Purinergic Signaling in Tumor-Associated Macrophages. Cytometry Part A, JUL 2020. Web of Science Citations: 0.
GLASER, TALITA; SHIMOJO, HIROMI; RIBEIRO, DEIDIANE ELISA; MARTINS, PATRICIA PEREIRA LOPES; BECO, RENATA PEREIRA; KOSINSKI, MICHAL; SAMPAIO, VANESSA FERNANDES ARNAUD; CORREA-VELLOSO, JULIANA; OLIVEIRA-GIACOMELLI, AGATHA; LAMEU, CLAUDIANA; DE JESUS SANTOS, ANA PAULA; DE SOUZA, HELLIO DANNY NOBREGA; TENG, YANG D.; KAGEYAMA, RYOICHIRO; ULRICH, HENNING. ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research. MOLECULAR PSYCHIATRY, APR 2020. Web of Science Citations: 0.
GLASER, TALITA; ARNAUD SAMPAIO, VANESSA FERNANDES; LAMEU, CLAUDIANA; ULRICH, HENNING. Calcium signalling: A common target in neurological disorders and neurogenesis. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 95, n. SI, p. 25-33, NOV 2019. Web of Science Citations: 4.
RIBEIRO, D. E.; GLASER, T.; OLIVEIRA-GIACOMELLI, A.; ULRICH, H. Purinergic receptors in neurogenic processes. Brain Research Bulletin, v. 151, n. SI, p. 3-11, SEP 2019. Web of Science Citations: 1.
RIBEIRO, DEIDIANE ELISA; RONCALHO, ALINE LULHO; GLASER, TALITA; ULRICH, HENNING; WEGENER, GREGERS; JOCA, SAMIA. P2X7 Receptor Signaling in Stress and Depression. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 11 JUN 1 2019. Web of Science Citations: 0.
MARTINEZ-RAMIREZ, A. S.; DIAZ-MUNOZ, M.; BATTASTINI, A. M.; CAMPOS-CONTRERAS, A.; OLVERA, A.; BERGAMIN, L.; GLASER, T.; MORITZ, C. E. JACINTHO; ULRICH, H.; VAZQUEZ-CUEVAS, F. G. Cellular Migration Ability Is Modulated by Extracellular Purines in Ovarian Carcinoma SKOV-3 Cells. Journal of Cellular Biochemistry, v. 118, n. 12, p. 4468-4478, DEC 2017. Web of Science Citations: 1.
GLASER, TALITA; HAN, INBO; WU, LIQUAN; ZENG, XIANG. Targeted Nanotechnology in Glioblastoma Multiforme. FRONTIERS IN PHARMACOLOGY, v. 8, MAR 31 2017. Web of Science Citations: 27.

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