Artículos de revistas
Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease
Fecha
2017-08Registro en:
Progress in Neurobiology 155 (2017) 96–119
10.1016/j.pneurobio.2015.09.012
Autor
Zucca, Fabio A.
Segura Aguilar, Juan
Ferrari, Emanuele
Muñoz Tapia, Patricia
Paris Pizarro, Irmgard
Sulzer, David
Sarna, Tadeusz
Casella, Luigi
Zecca, Luigi
Institución
Resumen
There are several interrelated mechanisms involving iron, dopamine, and neuromelanin in neurons.
Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine
neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal
populations most targeted in Parkinson’s disease. Many cellular redox reactions rely on iron, however an
altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson’s
disease patients are present. Dopamine accumulation can induce neuronal death; however, excess
dopamine can be removed by converting it into a stable compound like neuromelanin, and this process
rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the
neuromelanin-iron complex, since neuromelanin is an effective metal chelator. Neuromelanin serves to
trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron,
dopamine, and neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be
disrupted. Indeed, when neuromelanin-containing organelles accumulate high load of toxins and iron
during aging a neurodegenerative process can be triggered. In addition, neuromelanin released by
degenerating neurons activates microglia and the latter cause neurons death with further release of
neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration.
Considering the above issues, age-related accumulation of neuromelanin in dopamine neurons shows an
interesting link between aging and neurodegeneration.