TRAF6 and alfa-synuclein interaction and the subsequent modulation of signaling pathways

• Grant number: 11/10303-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2011
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Lidia Mitiko Yshii
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 13/22196-4 - The role of CD8 T cells on Paraneoplastic cerebellar degeneration, BE.EP.PD

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Although PD symptoms and neuropathology are well defined, its etiology is still unknown. Sporadic PD is pathologically characterized by the presence of Lewy bodies (LB) which are aggregated lipoprotein located inside the neuron. ±-synuclein (±-syn) is a soluble protein which is present in presynaptic terminals of various transmission systems. There are evidences suggesting that this protein is an essential component of LB found in dopaminergic neurons from nigrostrital system of PD patients. It is postulated that ±-syn has a key role in PD pathogenesis because it can affect dopaminergic neurons homeostasis, leading to increased dopamine (DA) in the cytosol and consequent oxidative stress. The nuclear transcription factor kappa B (NF-kappaB) participates in the regulation of immune and inflammatory responses, as well as cell death. NF k B may be stimulated by several factors including neurotransmitters, such as, dopamine and glutamate, stress and Beta-amyloid protein. TRAF6 (tumor necrosis factor receptor Associated factor 6) is a member of family of six TRAFs, which seems to interact with ubiquitin and ±-synuclein, because they are co-localized in LB. In this project, we intend to investigate the role of TRAF6 binding to ±-synuclein through activation of NF-kB in dopaminergic cells, as well as in cells obtained from primary culture of dorsal root of mice spinal cord. These results could bring new insight for the development of new therapeutic targets for treatment of neurodegenerative diseases. (AU)

Scientific publications

(4)

(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)

YSHII, LIDIA M.; MANFIOLLI, ADRIANA O.; DENADAI-SOUZA, ALEXANDRE; KINOSHITA, PAULA F.; GOMES, MARCELO D.; SCAVONE, CRISTOFORO. Tumor necrosis factor receptor-associated factor 6 interaction with alpha-synuclein enhances cell death through the Nuclear Factor-kB pathway. IBRO REPORTS, v. 9, p. 218-223, DEC 2020. (12/07784-4, 11/10303-5, 14/24951-7, 09/12375-3, 18/01308-2, 16/07427-8, 19/10044-1, 18/14289-6, 13/22196-4)

KINOSHITA, PAULA F.; YSHII, LIDIA M.; ORELLANA, ANA MARIA M.; PAIXAO, AMANDA G.; VASCONCELOS, ANDREA R.; LIMA, LARISSA DE SA; KAWAMOTO, ELISA M.; SCAVONE, CRISTOFORO. Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells. SCIENTIFIC REPORTS, v. 7, JUL 7 2017. (11/22844-0, 11/10303-5, 14/05026-0, 16/07376-4, 11/21308-8, 11/12255-8, 11/04327-9)

YSHII, LIDIA M.; DENADAI-SOUZA, ALEXANDRE; VASCONCELOS, ANDREA R.; AVELLAR, MARIA CHRISTINA W.; SCAVONE, CRISTOFORO. Suppression of MAPK attenuates neuronal cell death induced by activated glia-conditioned medium in alpha-synuclein overexpressing SH-SY5Y cells. JOURNAL OF NEUROINFLAMMATION, v. 12, OCT 26 2015. (11/10303-5, 11/12255-8, 09/12375-3)

VASCONCELOS, ANDREA RODRIGUES; KINOSHITA, PAULA FERNANDA; YSHII, LIDIA MITIKO; MARQUES ORELLANA, ANA MARIA; BOEHMER, ANA ELISA; LIMA, LARISSA DE SA; ALVES, ROSANA; ANDREOTTI, DIANA ZUKAS; MARCOURAKIS, TANIA; SCAVONE, CRISTOFORO; et al. Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus. NEUROBIOLOGY OF AGING, v. 36, n. 5, p. 1914-1923, MAY 2015. (11/10303-5)