Alterations of biochemical properties and functions of PrPc induced by endogenous dopamine metabolites and oligomeric amyloid beta peptide

• Grant number: 13/22413-5
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2014 - February 29, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Kil Sun Lee
• Grantee: Kil Sun Lee
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Hanna Karen Moreira Antunes ; Isaias Glezer

Abstract

The aging of modern society progressively increases the prevalence of neurodegenerative diseases, yet there is no cure. The accumulation of protein aggregates is a common feature of many neurodegenerative diseases and in most cases, protein aggregates occur without mutations in the gene or familiar or clinical history that explain the manifestation of the disease. This evidence corroborates the view that certain endogenous metabolites can induce the formation of protein aggregates triggering toxic signals to the cells. Therefore the identification of these pathways may help to elucidate the mechanisms of neurodegeneration.PrPC is highly expressed in central nervous system and its conformational changes have been pointed out as the main cause of transmissible spongiform encephalopathy. In addition to its involvement in the pathogenesis, PrPC can also play anti-oxidant roles, directly reacting with free radicals or modulate synaptic activity by interacting with various molecules such as laminin or mGluR5. However, several data allow us to speculate that the imbalance of certain metabolic pathways (which generate ligands of PrPC) can impair the beneficial function of PrPC, resulting in the accumulation of protein aggregates or synaptic dysfunction. Based on this hypothesis, this project aims to investigate the deleterious effects of alterations in biochemical properties and functions of PrPC induced by oxidative metabolites of dopamine and beta amyloid oligomers. Considering that most neurodegenerative diseases are sporadic, this study can help to elucidate how the accumulation of certain metabolites can cause neuronal death, and this information can be useful in identifying biomarkers and therapeutic targets. (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)

DA LUZ, MARCIO H. M.; PERES, ITALO T.; SANTOS, TIAGO G.; MARTINS, VILMA R.; ICIMOTO, MARCELO Y.; LEE, KIL S.. Dopamine induces the accumulation of insoluble prion protein and affects autophagic flux. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 9, FEB 2 2015. (13/22413-5, 12/18093-2, 08/06152-9, 09/14027-2)

MELLO DA LUZ, MARCIO HENRIQUE; GLEZER, ISAIAS; XAVIER, ANDRE MACHADO; PAIVA DA SILVA, MARCELO ALBERTI; MONTEIRO, JESSICA; PINO, VOLEJNIK; ZAMITH, THIAGO PANARO; VIEIRA, TAYNARA FERNANDA; ANTONIO, BRUNO BRITO; MOREIRA ANTUNES, HANNA KAREN; et al. Expression of Tyrosine Hydroxylase is Negatively Regulated Via Prion Protein. Neurochemical Research, v. 41, n. 7, p. 1691-1699, JUL 2016. (13/22413-5, 13/07937-8)

FRANK, MIRIAM KANNEBLEY; DE MELLO, MARCO TULIO; LEE, KIL SUN; DAUBIAN-NOSE, PAULO; TUFIK, SERGIO; ESTEVES, ANDREA MACULANO. Sleep-related movement disorder symptoms in SHR are attenuated by physical exercise and an angiotensin-converting enzyme inhibitor. Physiology & Behavior, v. 154, p. 161-168, FEB 1 2016. (13/22413-5, 11/21729-3)