Dopamine Oxidation Products as Mitochondrial Endotoxins, a Potential Molecular Mechanism for Preferential Neurodegeneration in Parkinson's Disease.
ACS Chem Neurosci
; 9(11): 2849-2858, 2018 11 21.
Article
en En
| MEDLINE
| ID: mdl-29906101
ABSTRACT
The preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta is responsible for the motor impairment associated with Parkinson's disease. Dopamine is a highly reactive molecule, which is usually stored inside synaptic vesicles where it is stabilized by the ambient low pH. However, free cytosolic dopamine can auto-oxidize, generating reactive oxygen species, and lead to the formation of toxic quinones. In the present work, we have analyzed the mechanisms through which the dysfunction of dopamine homeostasis could induce cell toxicity, by focusing in particular on the damage induced by dopamine oxidation products at the mitochondrial level. Our results indicate that dopamine derivatives affect mitochondrial morphology and induce mitochondrial membrane depolarization, leading to a reduction of ATP synthesis. Moreover, our results suggest that opening of the mitochondrial transition pore induced by dopamine-derived quinones may contribute to the specific Parkinson's disease-associated vulnerability of dopamine containing neurons.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Quinonas
/
Dopamina
/
Especies Reactivas de Oxígeno
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia