Degenerative and regenerative processes in Alzheimer's Disease: from cell culture to cell therapy

• Grant number: 17/12412-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Beatriz de Oliveira Monteiro
• Grantee: Beatriz de Oliveira Monteiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 19/15266-2 - Degenerative and regenerative processes in Alzheimer's Disease: from cell culture to cell therapy, BP.TT; 18/11616-6 - Degenerative and regenerative processes in Alzheimer's Disease: from cell culture to cell therapy, BP.TT

Abstract

Alzheimer´s disease (AD) is the most frequent cause of dementia worldwide. As the world population ages, the frequency is expected to double by 2030 and triple by 2050. Neither healthcare nor financial systems are prepared to face the magnitude of the situation, and is increasingly important the development of studies to better understand the causes and risk factors involved in AD, in addition to the search for new interventions that can help developing effective preventive and treatment strategies. Mesenchymal (MSC) and neural (NSC) stem cells are involved in imunorregulation, trophic mechanisms, proliferative and antiapoptotic actions, in addition to promote neurogenesis and angiogenesis, and could contribute to the regeneration of nervous tissue, reduction of ²-amyloid plaques deposition (²A) and stabilization of neurotrophin levels, constituting a promising strategy for the treatment of AD. Another emerging strategy that is being studied as a possible therapy in AD is physical exercise, which helps maintaining cognitive function, improvement in memory and learning, and decrease the risk of AD development. We propose to investigate the AD by means of studying the degenerative processes present during the development of the disease, and the regenerative and therapeutic possibilities. In vitro studies will make possible the investigation of neurospheres from AD animals in the presence of neurotrophins in the culture. The aspects involved in the formation of the spheres must help for better understanding of pathophysiological process. In turn by in vivo studies, mesenchymal and neural stem cells transplanted in the hippocampus of transgenic animals for AD (APP/PS1) submitted to resistance exercise should interfere in the levels of neurotrophic factors, formation of the ²A plaques, vascularization and inflammation, in addition to reducing the loss of memory and cognitive deficit. (AU)

Scientific publications

(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)

WUO-SILVA, RAPHAEL; FUKUSHIRO-LOPES, DANIELA F.; FIALHO, BRUNO P.; HOLLAIS, ANDRE W.; SANTOS-BALDAIA, RENAN; MARINHO, EDUARDO A. V.; MARI-KAWAMOTO, ELISA; YOKOYAMA, THAIS S.; LOPES-SILVA, LEONARDO B.; BERRO, LAIS F.; et al. Participation of Dopamine D1 and D2 Receptors in the Rapid-Onset Behavioral Sensitization to Modafinil. FRONTIERS IN PHARMACOLOGY, v. 10, MAR 11 2019. (17/12412-2)

CAMPOS, HENRIQUE C.; RIBEIRO, DEIDIANE ELISA; HASHIGUCHI, DEBORA; HUKUDA, DEBORAH Y.; GIMENES, CHRISTIANE; ROMARIZ, SIMONE A. A.; YE, QING; TANG, YONG; ULRICH, HENNING; LONGO, BEATRIZ MONTEIRO. Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer's Disease. STEM CELL REVIEWS AND REPORTS, JAN 2022. (17/12412-2, 18/07366-4)