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From Pancreatic ß-Cell Gene Networks to Novel Therapies for Type 1 Diabetes.
Eizirik, Decio L; Szymczak, Florian; Alvelos, Maria Inês; Martin, Frank.
Afiliación
  • Eizirik DL; Indiana Biosciences Research Institute, Indianapolis, IN deizirik@indianabiosciences.org.
  • Szymczak F; ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
  • Alvelos MI; ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
  • Martin F; ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.
Diabetes ; 70(9): 1915-1925, 2021 09.
Article en En | MEDLINE | ID: mdl-34417266
ABSTRACT
Completion of the Human Genome Project enabled a novel systems- and network-level understanding of biology, but this remains to be applied for understanding the pathogenesis of type 1 diabetes (T1D). We propose that defining the key gene regulatory networks that drive ß-cell dysfunction and death in T1D might enable the design of therapies that target the core disease mechanism, namely, the progressive loss of pancreatic ß-cells. Indeed, many successful drugs do not directly target individual disease genes but, rather, modulate the consequences of defective steps, targeting proteins located one or two steps downstream. If we transpose this to the T1D situation, it makes sense to target the pathways that modulate the ß-cell responses to the immune assault-in relation to signals that may stimulate the immune response (e.g., HLA class I and chemokine overexpression and/or neoantigen expression) or inhibit the invading immune cells (e.g., PDL1 and HLA-E expression)-instead of targeting only the immune system, as it is usually proposed. Here we discuss the importance of a focus on ß-cells in T1D, lessons learned from other autoimmune diseases, the "alternative splicing connection," data mining, and drug repurposing to protect ß-cells in T1D and then some of the initial candidates under testing for ß-cell protection.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Redes Reguladoras de Genes Límite: Humans Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Redes Reguladoras de Genes Límite: Humans Idioma: En Revista: Diabetes Año: 2021 Tipo del documento: Article País de afiliación: India Pais de publicación: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA