Development of C75-CoA loaded polymeric micelles targeting brain CPT1A: A novel nanomedicine-based approach to fight obesity and cancer
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Autor/a
García-Chica, Jesús
Otros/as autores/as
Rodríguez Rodríguez, Rosalía
Ariza Piquer, Xavier
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
Fecha de defensa
2024-02-14T19:38:56Z2024-02-14T19:38:56Z
2023-12-01
Resumen
Brain lipid metabolism has a key role in many physiological processes, and its malfunction is associated with a plethora of diseases, such as obesity and glioblastoma multiforme (GBM). Carnitine palmitoyl transferase 1A (CPT1A), an important protein in the fatty acid oxidation (FAO) pathway, has a prominent role in this association. In the brain, activation of CPT1A in hypothalamic neurons increases food intake and body weight in mice, while its inhibition causes the opposite effect, indicating its antiobesity potential. In GBM cells, overexpression of CPT1A and other lipid metabolism proteins has been described as a crucial pathway for GBM cell survival. Then, pharmacological inhibition of CPT1A and therefore fatty acid oxidation, could constitute a promising treatment for these diseases. However, targeting CPT1A in brain cells is difficult to reach with the current formulations in vivo. The racemic drug Compound 75 (C75) is a well-known CPT1A inhibitor when conjugated with Coenzyme A, but with important constraints such as polarity and low cell-permeability that limit the cellular uptake.
Tipo de documento
Tesis
Versión publicada
Lengua
English
Materias y palabras clave
Obesity
Glioblastoma Multiforme
Brain Lipid Metabolism
C75
PIC micelle
Nanocarrier
Metabolic disease
CPT1A
Hypothalamus
Arcuate nucleus
Ciències de la salut
616.8
Páginas
266 p.
application/pdf
Publicado por
Universitat Internacional de Catalunya
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http://creativecommons.org/licenses/by-nc-nd/4.0/