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Klotho effects on insulin signaling and energetic metabolism in the central nervous system

Grant number: 13/10787-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2013
Effective date (End): January 31, 2018
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Cristoforo Scavone
Grantee:Caio Henrique Yokoyama Mazucanti
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/09971-7 - Klotho protein and neuronal energy metabolism, BE.EP.DR


Ageing process was always investigated in C. elegans due to its reproductive cycle (they are hermaphrodites) and short lifespan (they live about 2 months). C. elegans life cycle can be indefinitely expanded once animals enter a phase known as dauer. Several genes altering this stage formation were identified and many codify for proteins associated with the only tyrosine kinase expressed in the animal. All of these genes have homologies in mammals and correspond to insulin signaling pathway. Negative modulation of this pathway leads to enhanced longevity in several animals, and vice-versa. Recently a novel protein associated with ageing was described in mammals. Mice lacking Klotho protein exhibit an early ageing phenotype, with several peripheral characteristics as well as central ones such as cognitive impairment. Since insulin signaling is associated with longevity, the objective of this work is to investigate the effects of Klotho protein upon insulin signaling in the central nervous system, evaluating some parameters associated with oxidative stress and energetic metabolism, considering that this parameters can be modulated by FoxO transcription factor which is modulated by insulin.

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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)
NAKAO, VINICIUS WANATABLE; YOKOWAMA MAZUCANTI, CAIO HENRIQUE; LIMA, LARISSA DE SA; DE MELLO, PALOMA SEGURA; DE SOUZA PORT'S, NATACHA MEDEIROS; KINOSHITA, PAULA FERNANDA; LEITE, JACQUELINE ALVES; KAWAMOTO, ELISA MITIKO; SCAVONE, CRISTOFORO. Neuroprotective action of alpha-Klotho against LPS-activated glia conditioned medium in primary neuronal culture. SCIENTIFIC REPORTS, v. 12, n. 1, p. 12-pg., . (13/10787-8, 18/14289-6)
CARARO-LOPES, MARINA MINTO; YOKOYAMA MAZUCANTI, CAIO HENRIQUE; SCAVONE, CRISTOFORO; KAWAMOTO, ELISA MITIKO; BERWICK, DANIEL CHARLES. The relevance of alpha-KLOTHO to the central nervous system: Some key questions. AGEING RESEARCH REVIEWS, v. 36, p. 137-148, . (16/07427-8, 13/10787-8, 14/14199-6, 11/21308-8)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MAZUCANTI, Caio Henrique Yokoyama. Effects of Klotho protein on insulin signaling and energy metabolism of the brain.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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