ß-N-methylamino-l-alanine is a non-competitive inhibitor of vesicular monoamine transporter 2.
Toxicon
; 222: 106978, 2023 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-36410456
ABSTRACT
The neurotoxic, non-proteinogenic amino acid ß-N-methylamino-l-alanine (BMAA) has been implicated in the development of neurodegenerative diseases; however, the mechanism(s) and mode(s) of toxicity remain unclear. Similarities in the neuropathology and behavioural deficits of neonatal rats exposed to either BMAA or reserpine, a known vesicular monoamine transporter 2 (VMAT2) inhibitor, suggest a similar mode of action. The aims of this study were therefore to determine if BMAA could prevent the uptake of serotonin into dense granules via inhibition of VMAT2, and, if so, the type of inhibition caused by BMAA. Exposing platelet dense granules to BMAA resulted in a concentration-dependent reduction in serotonin uptake. The inhibition of VMAT2 was non-competitive. The findings from this study support previous reports that BMAA-associated neuropathologies in a neonatal rat model may be due to VMAT2 inhibition during critical periods of neurogenesis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Vesiculares de Transporte de Monoamina
/
Diamino Aminoácidos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article