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Klotho protein and neuronal energy metabolism

Grant number: 16/09971-7
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): July 11, 2016
Effective date (End): July 10, 2017
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristoforo Scavone
Grantee:Caio Henrique Yokoyama Mazucanti
Supervisor abroad: Mark Mattson
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : National Institutes of Health, Baltimore (NIH), United States  
Associated to the scholarship:13/10787-8 - Klotho effects on insulin signaling and energetic metabolism in the central nervous system, BP.DR

Abstract

Aging 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 of these genes codify proteins associated with the only tyrosine kinase receptor expressed in the animal. All of these genes have homologies in mammals and correspond to insulin signaling pathway enzymes. Negative modulation of this pathway leads to enhanced longevity in several animals, while its upregulation has the opposite effect. Recently, a novel protein associated with ageing was described in mammals. Mice lacking Klotho protein exhibit an early aging 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 redox state, energy metabolism and vulnerability to amyloid beta-peptide, mitochondrial toxins and excitotoxins. (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)
MAZUCANTI, CAIO H.; KAWAMOTO, ELISA M.; MATTSON, MARK P.; SCAVONE, CRISTOFORO; CAMANDOLA, SIMONETTA. Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, v. 39, n. 8, p. 1544-1556, AUG 2019. Web of Science Citations: 0.

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