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Cell mechanisms of neuroprotection in an Alzheimer's-like model of dementia: modulation by calcium and autophagy study

Grant number: 10/08437-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Soraya Soubhi Smaili
Grantee:Letícia Rodrigues
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

Streptozotocin (STZ) is a drug that has been used via intracerebroventricular (ICV) to induce a model of Alzheimer's disease (AD)-type sporadic in rodents. The sporadic type of AD is closely associated with aging without specific gene alterations. Among some characteristics of the disease obtained with STZ there are cognitive deficits, neuronal loss, astrogliosis and oxidative stress. We still do not know many of the mechanisms leading to these changes being necessary to seek alternative therapies to combat or minimize the symptoms related to these changes. Autophagy is a process that takes place in all cells under physiological conditions and during aging. It is also present in the establishment of neurodegenerative diseases and it may function as a neuroprotective process that allows removal of toxic protein aggregates. Autophagy was also shown to be modulated by calcium signaling and calcium storage by different organelles. Little is known about autophagy in AD, especially in the model obtained with STZ. Therefore, this work proposes a study of molecular mechanisms, biochemical and cellular relationship between autophagy, apoptosis and calcium homeostasis in an AD model. This will be obtained by in vivo and in vitro treatments with STZ. In addition, the possible neuroprotective effect of guanosine in the process will be studied. (AU)