Casein kinase 1 as a target for drug design in Alzheimer's Disease

• Grant number: 10/14929-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2011
• Effective date (End): February 28, 2014
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Carlos Henrique Tomich de Paula da Silva
• Grantee: Ricardo Pereira Rodrigues
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by atrophy of cortex and loss of cortical and subcortical neurons. Several kinases, including casein kinase 1 (CK1), affect the conformations of Alzheimer's proteins, such as B-amyloid and Tau. Recent data indicate the presence of CK1 isoforms in vacuolar strands and granulomatous lesions in Alzheimer's brain. The CK1 as a new therapeutic target is a viable alternative, without the usual side effects. In this new approach, the B-amyloid (BACE and gama-secretase) key enzymes are targets of CK1, and its suppression decreases B-amyloid production without interfere in other enzymatic processes. In CK1's known inhibitors research, a pharmacophoric pattern can be found and applied in potential compounds, keeping pharmacophoric features. The rational drug design based on structure, efficient and less costly methodology, were used in new drugs development. (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)

RODRIGUES, RICARDO P.; DA SILVA, CARLOS H. T. P.. Discovery of potential neurodegenerative inhibitors in Alzheimer's disease by casein kinase 1 structure-based virtual screening. MEDICINAL CHEMISTRY RESEARCH, v. 26, n. 12, p. 3274-3285, DEC 2017. (10/14929-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Ricardo Pereira. Casein kinase 1 as a target for drug design in Alzheimer\'s disease. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.