Evaluation of ADAM10 activity in different cellular fractions

• Grant number: 19/26444-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2020
• End date: February 28, 2022
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Maria Patrícia Oliveira Monteiro e Pereira de Almeida
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Alzheimer's disease (AD) is the type of dementia with the highest incidence worldwide, as well as in Brazil. Its main pathogenic characteristic is the accumulation and aggregation of beta amyloid peptide (²A) in the brain, together with other pathological milestones, such as hyperphosphorylation of Tau protein. The two molecules in excess or with altered structures form the extracellular senile plaques and intracellular neurofibrillary tangles, respectively. ADAM10 (disintegrin and metalloproteinase) is of great importance for cellular processes such as cellular communication and signaling, along with signal transmission between neurons. This protein has several domains, which are responsible for its activity and localization in the neuronal membrane, for example. Some studies in the literature report that ADAM10, when inserted into the membrane, is responsible for cleavage of APP (amyloid precursor protein), preventing the formation of ²A by non-amyloidogenic cleavage pathway and, therefore, being the target of many studies. Therefore, the active form would be anchored to the membranes, such as platelets and neuronal cells. In this sense, this project aims to evaluate the activity of ADAM10 in different cell fractions, such as cell membrane and cytoplasm, in order to prove this hypothesis. The results of this study may help to better understand the physiology of ADAM10 and its function as a biomarker of AD. (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)