Proteomic analysis of neuromelanin granules in normal aging and Parkinson disease

• Grant number: 10/06521-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2010
• End date: July 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Lea Tenenholz Grinberg
• Grantee: Renata Elaine Paraizo Leite
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Although many brain areas exhibit the neuropathological signs of Parkinson's disease (PD), the loss of cells containing neuromelanin in the substantia nigra is a cardinal diagnostic criteria for PD. Currently, many questions remain unanswered about the neuromelanin, but its presence as a basic characteristic of a group of vulnerable cells suggests a role of this pigment in the pathophysiology of PD. Thus, in order to understand the structure and function of neuromelanin and to identify proteins that are altered in PD, we propose a collaborative project using samples of the substance nigra of the Human Brain Bank of the Aging Brain Study Group (HBB-ABSG), Sao Paulo University Medical School. Will be analyzed 50 cases encompassing PD and control, of both genders, aged over 50 years. Neuromelanin granules will be isolated in Brazil using subcellular fractionation. The quality of isolated granules and preservation of ultrastructural characteristics will be monitored by electron microscopy. Procedures for the identification of proteins will be performed at the Medical Proteome Center at the University of Bochum in Germany and will include 1D SDS-PAGE, Western blot and mass spectrometry. No identifying data of the subject sample will be sent abroad. Antibodies for detection of altered proteins will be produced at the end of the work. These antibodies will be validated in tissue by immunohistochemistry, in Brazil. Adding to the fact that there are no adequate animal models that reproduce all the pathophysiology of PD, neuromelanin is absent in the brains of many non-human species, which makes mandatory the use of human tissue in this work. In addition, proteomic method is incipient in Brazil and still very expensive, which makes this collaboration a unique opportunity for understanding the structure and function of neuromelanin and to identify proteins that are altered in PD.

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)

RODRIGUEZ, ROBERTA DIEHL; SUEMOTO, CLAUDIA KIMIE; MOLINA, MARIANA; NASCIMENTO, CAMILA FERNANDES; LEITE, RENATA ELAINE PARAIZO; DE LUCENA FERRETTI-REBUSTINI, RENATA ELOAH; FARFEL, JOSE MARCELO; HEINSEN, HELMUT; NITRINI, RICARDO; UEDA, KENJI; et al. d Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, v. 75, n. 7, p. 628-635, JUL 2016. (11/19833-7, 10/06521-4, 12/07526-5)

NASCIMENTO, CAMILA; SUEMOTO, CLAUDIA K.; RODRIGUEZ, ROBERTA D.; DI LORENZO ALHO, ANA TEREZA; LEITE, RENATA P.; FARFEL, JOSE MARCELO; GONCALVES PASQUALUCCI, CARLOS AUGUSTO; JACOB-FILHO, WILSON; GRINBERG, LEA T.. Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample. Brain Pathology, v. 26, n. 2, p. 177-185, MAR 2016. (11/19833-7, 10/06521-4, 12/07526-5)