Expression and activity of ADAM10 and levels of insulinic route proteins in neuroblastoma cells under hyperglycemic and normoglycemic conditions

• Grant number: 21/01906-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2021
• End date: May 31, 2023
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Marina Mantellatto Grigoli
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 21/01863-9 - Biology and function of ADAM10 isoforms for differential diagnosis of Alzheimer's Disease by electrochemical sensors, AP.TEM

Abstract

Alzheimer's disease (AD) is a gradual and progressive neurodegenerative disease characterized by predominant cortical atrophy of the medial temporal lobe and microscopically, by extensive neuronal losses and deposits called neurofibrillary tangles and senile plaques. Since the results of the Rotterdam studies in 1992, type 2 Diabetes mellitus (DM2) has been known to increase the risk of dementia. Patients with DM2 show structural brain changes and cognitive impairment with a high risk of developing AD. These results suggest that insulin can play one fundamental role in relation to brain activity and memory formation. From these findings, the AD has been called by some researchers "Diabetes type 3" (DM3) or "brain diabetes". Some search groups show that ADAM10 (ADisintegrin And Metalloprotease), the alfa secretase that inhibits the formation of the senile plaques and therefore, is protective against AD, and is altered in the blood of the elderly with this dementia when compared with cognitive healthy elderly. In this sense, the objective of this study is to check ifa difference at ADAM10 levels and activity exists in neuroblastoma cells (SH-SY5Y) cultivated in normal middle cellular and hyperglycemic, in one condition that simulates the DM2 as well as concurrent alterations of proteins levels involved in the insulin route. The clinical impact of this studyit is related to the best clinical approaches to treating Alzheimer´s disease observing the metabolicstate the patients. (AU)

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)

MANZINE, PATRICIA R.; VATANABE, IZABELA P.; GRIGOLI, MARINA M.; PEDROSO, RENATA, V; MONTEIRO, MARIA PATRICIA A. O.; OLIVEIRA, DANIELLE S. M. S.; NASCIMENTO, CARLA M. C.; PERON, RAFAELA; ORLANDI, FABIANA S.; COMINETTI, MARCIA R.. Potential Protein Blood-based Biomarkers in Different Types of Dementia: A Therapeutic Overview. CURRENT PHARMACEUTICAL DESIGN, v. 28, n. 14, p. 17-pg., 2022-01-01. (19/26709-2, 19/26444-9, 14/21066-2, 21/01906-0, 16/06226-9, 19/02648-4, 17/18808-5, 20/12915-7, 18/05446-0)