Neuronal Proteins as Targets of 3-Hydroxykynurenine: Implications in Neurodegenerative Diseases.
ACS Chem Neurosci
; 10(8): 3731-3739, 2019 08 21.
Article
en En
| MEDLINE
| ID: mdl-31298828
The neurotoxic activity of the tryptophan metabolite 3-hydroxykynurenine (3OHKyn) in neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, is related to oxidative stress and 3OHKyn interaction with cellular proteins. The pattern of protein modification induced by 3OHKyn involves the nucleophilic side chains of Cys, His, and Lys residues, similarly to the one promoted by dopamine and other catecholamines. In the present work, we have analyzed the reactivity of 3OHKyn toward the neuronal targets α-synuclein (and its N-terminal fragments 1-6 and 1-15) and amyloid-ß peptides (1-16 and 1-28) and characterized the resulting conjugates through spectrometric (LC-MS/MS) and spectroscopic (UV-vis, fluorescence, NMR) techniques. The amino acid residues of α-synuclein and amyloid-ß peptides involved in derivatizations by 3OHKyn and its autoxidation products (belonging to the xanthommatin family) are Lys and His, respectively. The pattern of protein modification is expanded in the conjugates obtained in the presence of the metal ions copper(II) or iron(III), reflecting a more oxidizing environment that in addition to adducts with protein/peptide residues also favors the fragmentation of the protein. These results open the perspective to using the 3OHKyn-protein/peptide synthetic conjugates to explore their competence to activate microglia cell cultures as well as to unravel their role in neuroinflammatory conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
/
Alfa-Sinucleína
/
Quinurenina
/
Neuronas
Límite:
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos