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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Tumor necrosis factor receptor-associated factor 6 interaction with alpha-synuclein enhances cell death through the Nuclear Factor-kB pathway

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Author(s):
Yshii, Lidia M. [1] ; Manfiolli, Adriana O. [2] ; Denadai-Souza, Alexandre [3] ; Kinoshita, Paula F. [1] ; Gomes, Marcelo D. [2] ; Scavone, Cristoforo [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, ICB 1, Ave Prof Lineu Prestes 1524, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, BR-04044020 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: IBRO REPORTS; v. 9, p. 218-223, DEC 2020.
Web of Science Citations: 0
Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by intracellular inclusions named Lewy bodies (LB), and alpha-synuclein (asyn) is the major component of these protein aggregates. The precise physiological and pathological roles of asyn are not fully understood. Nevertheless, asyn present in LB is ubiquitinated but fails to reach the 26S proteasome. The mutation A30 P is related to an aggressive and early-onset form of PD. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase, and it interacts and ubiquitinates the asyn in atypical chains (lysine K6, K27, K29, and K33). Methods: Here, we investigated the role of TRAF6 interaction with asyn and the involvement of nuclear factor kappa B (NF-kappa B), a key transcription factor in pro-inflammatory signaling pathway activation. Results and Conclusion: We demonstrated that TRAF6 binds to both WT and the mutant form A30 P asyn in an SH-SY5Y cell model. Additionally, the interaction between TRAF6 and WT asyn induced an increase in the activation of NF-kappa B, leading to changes in TNF, IL-1 beta and IL-10 levels and culminating in reduced cell viability. Interestingly, the activation of NF-kappa B and gene regulation were not found in A30 P asyn. These data point to a novel role of TRAF6 in the pathophysiology of PD. (AU)

FAPESP's process: 12/07784-4 - Analysis of the effect of heterologous expression of hSPAG11B alternative splice variants in the development of inflammatory arthritis in the knee joint of wild-type and F2rl1 (PAR2) knockout mice
Grantee:Alexandre Denadai Souza
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 11/10303-5 - TRAF6 and alfa-synuclein interaction and the subsequent modulation of signaling pathways
Grantee:Lidia Mitiko Yshii
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/24951-7 - Identification of targets regulated by Aspergillus fumigatus phosphatase PhzA
Grantee:Adriana Oliveira Manfiolli
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 09/12375-3 - Role of the protein SPAG11 in the modulation of experimental arthritis
Grantee:Alexandre Denadai Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/01308-2 - Genes Differentially Expressed During Reversion Skeletal Muscle Atrophy
Grantee:Marcelo Damário Gomes
Support Opportunities: Regular Research Grants
FAPESP's process: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system
Grantee:Cristoforo Scavone
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 19/10044-1 - Study of the modulator role of Klotho protein in neuroinflammatory signaling in mice
Grantee:Jessika Cristina Bridi
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 18/14289-6 - The role of Klotho protein in Alzheimer's disease
Grantee:Paula Fernanda Kinoshita
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 13/22196-4 - The role of CD8 T cells on Paraneoplastic cerebellar degeneration
Grantee:Lidia Mitiko Yshii
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor