Huntington's disease: Huntingtin roles during cell fate decision

• Grant number: 15/13345-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2015
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Talita Glaser
• Host 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

(20)

(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)

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. (12/50880-4, 15/13345-1)

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; et al. 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. (18/07366-4, 12/50880-4, 15/13345-1)

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. (15/13345-1, 12/50880-4, 16/07659-6)

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. (15/13345-1, 18/17504-5, 19/24553-5, 15/19128-2, 18/07366-4)

ANDREJEW, ROBERTA; GLASER, TALITA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE; GODOY, MARIANA; GRANATO, ALESSANDRO; ULRICH, HENNING; RATAJCZAK, MZ. Targeting Purinergic Signaling and Cell Therapy in Cardiovascular and Neurodegenerative Diseases. STEM CELLS: THERAPEUTIC APPLICATIONS, v. 1201, p. 79-pg., 2019-01-01. (18/08426-0, 19/05384-8, 15/13345-1, 12/50880-4)

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, v. 97, n. 11, JUL 2020. (17/06132-7, 15/13345-1, 18/07366-4, 18/14993-5, 15/19128-2)

GLASER, TALITA; OLIVEIRA-GIACOMELLI, AGATHA; PETIZ, LYVIA LINTZMAIER; RIBEIRO, DEIDIANE ELISA; ANDREJEW, ROBERTA; ULRICH, HENNING. Antagonistic Roles of P2X7 and P2Y2 Receptors in Neurodegenerative Diseases. FRONTIERS IN PHARMACOLOGY, v. 12, p. 7-pg., 2021-04-12. (18/08426-0, 18/17504-5, 19/24553-5, 19/26852-0, 15/13345-1, 18/07366-4)

RIBEIRO, D. E.; GLASER, T.; OLIVEIRA-GIACOMELLI, A.; ULRICH, H.. Purinergic receptors in neurogenic processes. Brain Research Bulletin, v. 151, p. 9-pg., 2019-09-01. (15/13345-1, 12/50880-4)

GLASER, TALITA; ANDREJEW, ROBERTA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE ELISA; MARQUES, LUCAS BONFIM; YE, QING; REN, WEN-JING; SEMYANOV, ALEXEY; ILLES, PETER; TANG, YONG; et al. Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease. NEUROSCIENCE BULLETIN, v. 36, n. 11, SI, p. 1299-1314, NOV 2020. (18/17504-5, 19/24553-5, 15/13345-1, 19/26852-0, 18/07366-4)

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. (15/13345-1, 12/50880-4, 18/08426-0)

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. (12/50880-4, 15/13345-1, 15/19128-2)

PETIZ, LYVIA LINTZMAIER; GLASER, TALITA; SCHARFSTEIN, JULIO; RATAJCZAK, MARIUSZ Z.; ULRICH, HENNING. P2Y14 Receptor as a Target for Neutrophilia Attenuation in Severe COVID-19 Cases: From Hematopoietic Stem Cell Recruitment and Chemotaxis to Thrombo-inflammation. STEM CELL REVIEWS AND REPORTS, v. 17, n. 1, SI, FEB 2021. (18/07366-4, 15/13345-1)

RIBEIRO, DEIDIANE ELISA; OLIVEIRA-GIACOMELLI, AGATHA; GLASER, TALITA; ARNAUD-SAMPAIO, VANESSA F.; ANDREJEW, ROBERTA; DIECKMANN, LUIZ; BARANOVA, JULIANA; LAMEU, CLAUDIANA; RATAJCZAK, MARIUSZ Z.; ULRICH, HENNING. Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. MOLECULAR PSYCHIATRY, v. 26, n. 4, DEC 2020. (18/17504-5, 19/24553-5, 15/19128-2, 15/13345-1, 19/26852-0, 18/07366-4)

PETIZ, LYVIA LINTZMAIER; GLASER, TALITA; SCHARFSTEIN, JULIO; RATAJCZAK, MARIUSZ Z.; ULRICH, HENNING. P2Y14 Receptor as a Target for Neutrophilia Attenuation in Severe COVID-19 Cases: From Hematopoietic Stem Cell Recruitment and Chemotaxis to Thrombo-inflammation. STEM CELL REVIEWS AND REPORTS, v. 17, n. 1, p. 12-pg., 2021-02-11. (18/07366-4, 15/13345-1)

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; et al. ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research. MOLECULAR PSYCHIATRY, v. 26, n. 6, p. 2633-2650, JUN 2021. (18/07366-4, 15/13345-1, 12/50880-4)

GLASER, TALITA; HAN, INBO; WU, LIQUAN; ZENG, XIANG. Targeted Nanotechnology in Glioblastoma Multiforme. FRONTIERS IN PHARMACOLOGY, v. 8, MAR 31 2017. (15/13345-1, 16/07659-6)

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, p. 26-pg., 2019-06-01. (18/08426-0, 15/13345-1, 12/50880-4)

GLASER, TALITA; ANDREJEW, ROBERTA; OLIVEIRA-GIACOMELLI, AGATHA; RIBEIRO, DEIDIANE ELISA; MARQUES, LUCAS BONFIM; YE, QING; REN, WEN-JING; SEMYANOV, ALEXEY; ILLES, PETER; TANG, YONG; et al. Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease. NEUROSCIENCE BULLETIN, v. 36, n. 11, p. 16-pg., 2020-10-07. (18/17504-5, 19/24553-5, 15/13345-1, 19/26852-0, 18/07366-4)

GONCALVES, MARIA CAROLINA BITTENCOURT; GLASER, TALITA; OLIVEIRA, SOPHIA LA BANCA DE; ULRICH, HENNING. Adenosinergic-Dopaminergic Signaling in Mood Disorders: A Mini-Review. JOURNAL OF CAFFEINE AND ADENOSINE RESEARCH, v. 10, n. 3, p. 10-pg., 2020-09-01. (18/07366-4, 15/13345-1)

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, p. 9-pg., 2019-11-01. (15/19128-2, 15/13345-1, 12/50880-4)