Molecular and Cellular Characterization of SIRT1 Allosteric Activators.
Methods Mol Biol
; 1983: 133-149, 2019.
Article
em En
| MEDLINE
| ID: mdl-31087296
ABSTRACT
SIRT1 is an NAD+-dependent lysine deacetylase that promotes healthy aging and longevity in diverse organisms. Small molecule allosteric activators of SIRT1 such as resveratrol and SRT2104 directly bind to the N-terminus of SIRT1 and lower the Km for the protein substrate. In rodents, sirtuin-activating compounds (STACs) protect from age-related diseases and extend life span. In human clinical trials, STACs have a high safety profile and anti-inflammatory activities. Here, we describe methods for identifying and characterizing STACs, including production of recombinant protein, in vitro assays with recombinant protein, and cellular assays based on mitochondrial dynamics. The methods described in this chapter will facilitate this discovery of improved STACs, natural and synthetic, in the pursuit of interventions to treat age-related diseases.
Palavras-chave
ADP-ribose; Aging; Allosteric activator; Deacetylase; Deacylase; Epigenetics; Histone; Histone deacetylase (HDAC); Longevity; Membrane potential; Metabolism; Mitochondria; NAD+; Nicotinamide; Reactive oxygen species (ROS); Recombinant protein; Resveratrol; SIRT1; Sirtuin; Sirtuin-activating compound (STAC); p53
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bioensaio
/
Regulação Alostérica
/
Descoberta de Drogas
/
Sirtuína 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article