Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice.
Proc Natl Acad Sci U S A
; 113(13): 3428-35, 2016 Mar 29.
Article
en En
| MEDLINE
| ID: mdl-26929359
Disrupted brain iron homeostasis is a common feature of neurodegenerative disease. To begin to understand how neuronal iron handling might be involved, we focused on dopaminergic neurons and asked how inactivation of transport proteins affected iron homeostasis in vivo in mice. Loss of the cellular iron exporter, ferroportin, had no apparent consequences. However, loss of transferrin receptor 1, involved in iron uptake, caused neuronal iron deficiency, age-progressive degeneration of a subset of dopaminergic neurons, and motor deficits. There was gradual depletion of dopaminergic projections in the striatum followed by death of dopaminergic neurons in the substantia nigra. Damaged mitochondria accumulated, and gene expression signatures indicated attempted axonal regeneration, a metabolic switch to glycolysis, oxidative stress, and the unfolded protein response. We demonstrate that loss of transferrin receptor 1, but not loss of ferroportin, can cause neurodegeneration in a subset of dopaminergic neurons in mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neuronas Dopaminérgicas
/
Hierro
/
Degeneración Nerviosa
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2016
Tipo del documento:
Article
Pais de publicación:
Estados Unidos