Scholarship 21/00270-4 - Inflamação, Neuroinflamação - BV FAPESP
Advanced search
Start date
Betweenand

Role of the protein Annexin A1 in the experimental model of Parkinsons Disease

Grant number: 21/00270-4
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Start date until: August 01, 2022
Status:Discontinued
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Cristiane Damas Gil
Grantee:Luiz Philipe de Souza Ferreira
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):24/05491-7 - Exploring the effects of annexin A1 interactions with NLRP3 in an ex vivo model of Alzheimer's disease: unravelling the dynamics of neuroinflammation and potential therapeutic implications, BE.EP.DD

Abstract

Parkinson's Disease (PD) is a neurodegenerative disorder of high incidence in the global population, which affects men and women mainly between 45 - 54 years-old. Recent studies demonstrate that neuroinflammation is a crucial condition of PD, prompting the search for more effective treatments with a focus on inflammation. In this context, we highlight Annexin A1 (AnxA1), an anti-inflammatory protein able to regulate neuroinflammation and activation of the NLRP3 inflammasome, a cytoplasmic sensor that acts on the progression of PD. So far, these mechanisms have not been explored in a PD model. Thus, we will evaluate the role of AnxA1 in a PD murine model induced by the neurotoxin 6-hydroxidopamine (6-OHDA). Male and female C57Bl/6 wild-type (WT) mice and knockouts for AnxA1 protein (AnxA1-/-), will be distributed in three groups (n =12/group): Sham, 6-OHDA+Saline and 6-OHDA+Ac2-26 (mimetic peptide of the N-terminal region of AnxA1). The 6-OHDA+Saline and 6-OHDA+Ac2-26 groups will undergo stereotactic surgery for infusion of 6-OHDA into the striatum (CPu). Then, 1 ¼L of 6-OHDA (5¼g/¼L) in saline solution with 0.1% ascorbic acid will be administered through an infusion needle into the right CPu (ipsilateral). The left CPu (control; contralalteral) will receive 1 ¼L of vehicle solution (saline with 0.1% ascorbic acid). The Sham group will receive only saline in the ipsi and contralateral CPu. The 6-OHDA+Ac2-26 group will receive 1 dose of Ac2-26 (100 µg/animal, i.p.) immediately after the 6-OHDA infusion, followed by 6 more daily doses of peptide. The 6-OHDA+Saline group will receive only saline. The Naive group will be only manipulated. The effect of the absence of AnxA1 and pharmacological treatment with Ac2-26 will be observed by behavioral testing. We will histologically evaluate the CPu and the Substantia Nigra (SN) of the midbrain, especially neurons, microglia (Iba-1) and astrocytes (GFAP); the expression pattern and possible colocalization of AnxA1, Fpr2, and NLRP3 in astrocytes and microglia by immunohistochemistry and immunofluorescence; mRNA levels of AnxA1, Fpr2, ASC, caspase 1, NLRP3, and alpha-synuclein genes by RT-PCR; expression of ERK/MAPK kinase, caspase 1 and IL-1b by western blotting in CPu and SN; peripheral blood leukocyte profile by flow cytometry; levels of cytokines (TNF-alpha, IL-1b, IL-6, IL-10 and MCP-1), and beta-amyloid peptide by multiplex assay. The studies will contribute to a better understanding of the mechanisms of action of AnxA1 and its peptide, as well as their possible therapeutic applications in PD. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

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)
LUIZ PHILIPE DE SOUZA FERREIRA; RAFAEL ANDRÉ DA SILVA; MATHEUS MARQUES MESQUITA DA COSTA; VINICIUS MORAES DE PAIVA RODA; SANTIAGO VIZCAINO; NILMA R.L.L. JANISSET; RENATA RAMOS VIEIRA; JOSÉ MARCOS SANCHES; JOSÉ MARIA SOARES JUNIOR; MANUEL DE JESUS SIMÕES. Sex differences in Parkinson’s Disease: An emerging health question. Clinics, v. 77, . (21/00270-4)
FERREIRA, LUIZ PHILIPE DE SOUZA; DA SILVA, RAFAEL ANDRE; GIL, CRISTIANE D.; GEISOW, MICHAEL J.. Annexin A1, A2, A5, and A6 involvement in human pathologies. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, v. N/A, p. 14-pg., . (21/00270-4, 22/02327-6, 22/12027-0)
DE SOUZA FERREIRA, LUIZ PHILIPE; DA SILVA, RAFAEL ANDRE; MESQUITA DA COSTA, MATHEUS MARQUES; DE PAIVA RODA, VINICIUS MORAES; VIZCAINO, SANTIAGO; JANISSET, NILMA R. L. L.; VIEIRA, RENATA RAMOS; SANCHES, JOSE MARCOS; SOARES JUNIOR, JOSE MARIA; SIMOES, MANUEL DE JESUS. Sex differences in Parkinson's Disease: An emerging health question. Clinics, v. 77, p. 3-pg., . (21/00270-4)
DA SILVA, RAFAEL ANDRE; DE PAIVA RODA, VINICIUS MORAES; DE SOUZA FERREIRA, LUIZ PHILIPE; OLIANI, SONIA M.; GIROL, ANA PAULA; GIL, CRISTIANE D.. Annexins as potential targets in ocular diseases. DRUG DISCOVERY TODAY, v. 27, n. 11, p. 9-pg., . (21/00270-4)

Please report errors in scientific publications list using this form.