Potential therapeutic applications of AKAP disrupting peptides.
Clin Sci (Lond)
; 134(24): 3259-3282, 2020 12 23.
Article
en En
| MEDLINE
| ID: mdl-33346357
ABSTRACT
The 3'-5'-cyclic adenosine monophosphate (cAMP)/PKA pathway represents a major target for pharmacological intervention in multiple disease conditions. Although the last decade saw the concept of highly compartmentalized cAMP/PKA signaling consolidating, current means for the manipulation of this pathway still do not allow to specifically intervene on discrete cAMP/PKA microdomains. Since compartmentalization is crucial for action specificity, identifying new tools that allow local modulation of cAMP/PKA responses is an urgent need. Among key players of cAMP/PKA signaling compartmentalization, a major role is played by A-kinase anchoring proteins (AKAPs) that, by definition, anchor PKA, its substrates and its regulators within multiprotein complexes in well-confined subcellular compartments. Different tools have been conceived to interfere with AKAP-based protein-protein interactions (PPIs), and these primarily include peptides and peptidomimetics that disrupt AKAP-directed multiprotein complexes. While these molecules have been extensively used to understand the molecular mechanisms behind AKAP function in pathophysiological processes, less attention has been devoted to their potential application for therapy. In this review, we will discuss how AKAP-based PPIs can be pharmacologically targeted by synthetic peptides and peptidomimetics.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proteínas de Anclaje a la Quinasa A
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Sci (Lond)
Año:
2020
Tipo del documento:
Article
País de afiliación:
Italia