Prevention and restoration of lactacystin‐induced nigrostriatal dopamine neuron degeneration by novel brain‐permeable iron chelators

2007 ◽  
Vol 21 (14) ◽  
pp. 3835-3844 ◽  
Author(s):  
Wen Zhu ◽  
Wenjie Xie ◽  
Tianhong Pan ◽  
Pingyi Xu ◽  
Mati Fridkin ◽  
...  
Keyword(s):  
Dopamine Neuron ◽  
Iron Chelators ◽  
Neuron Degeneration ◽  
Nigrostriatal Dopamine ◽  
Permeable Iron

Neuromelanin and Nigrostriatal Dopamine Neuron Degeneration

1993 ◽  
Vol 60 (5) ◽  
pp. 1976-1977 ◽  
Author(s):  
K. Jellinger ◽  
E. Kienzl ◽  
G. Rumpelmair ◽  
P. Riederer ◽  
H. Stachelberger ◽  
...  
Keyword(s):  
Dopamine Neuron ◽  
Neuron Degeneration ◽  
Nigrostriatal Dopamine

scholarly journals Control of the Nigrostriatal Dopamine Neuron Activity and Motor Function by the Tail of the Ventral Tegmental Area

2014 ◽  
Vol 39 (12) ◽  
pp. 2788-2798 ◽  
Author(s):  
Romain Bourdy ◽  
María-José Sánchez-Catalán ◽  
Jennifer Kaufling ◽  
Judith J Balcita-Pedicino ◽  
Marie-José Freund-Mercier ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Motor Function ◽  
Dopamine Neuron ◽  
Neuron Activity ◽  
Nigrostriatal Dopamine ◽  
Ventral Tegmental

Iron Chelation by Deferoxamine Induces Autophagy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 117-117 ◽  
Author(s):  
Ivana De Domenico ◽  
Diane McVey Ward ◽  
James P. Kushner ◽  
Jerry Kaplan
Keyword(s):  
Molecular Weight ◽  
Iron Overload ◽  
Iron Chelation ◽  
Iron Chelators ◽  
Immunochemical Analysis ◽  
Alternate Route ◽  
High Affinity ◽  
Secondary Iron Overload ◽  
Proteosomal Degradation ◽  
Permeable Iron

Abstract Deferoxamine (DFO) is a high affinity Fe (III) chelator produced by Streptomyces pilosus that is used clinically to remove systemic iron in secondary iron overload disorders. DFO cannot be absorbed through the intestine and must be injected. As shown previously, De Domenico et al. EMBO J (2006), expression of Ferroportin (Fpn), the only mammalian iron exporter, can deplete cells of ferritin by lowering cytosolic iron and by exporting iron from cells. Fpn-mediated iron loss induces ferritin degradation by the proteosome. In this study we show that permeable iron chelators, desferirax or deferriprone also induce the proteosomal degradation of ferritin. In contrast, DFO-mediated iron chelation at clinically useful concentrations, leads to ferritin degradation in lysosomes. Immunochemical analysis revealed that DFO-treated cells show increased levels of LC3B, a protein required for autophagy, suggesting that DFO induces autophagy. Treatment of cells with desferasirox or deferriprone did not lead to accumulation of LC3B. Studies using high molecular weight conjugates of DFO or inhibitors of endocytosis showed that the presence of DFO in lysosomes was responsible for the induction of autophagy. Incubation of DFO-treated cells with 3-methyladenine, an autophagy inhibitor, does not, however, prevent ferritin loss suggesting there may be an alternate route for ferritin degradation. This hypothesis was confirmed by examining the effect of the proteosome inhibitor, MG132, on DFOinduced autophagy in cells treated with DFO and 3-methyladenine. Addition of MG132 to 3-methyladenine treated cells prevents ferritin degradation. These results indicate that ferritin degradation occurs by two routes: a DFO-induced entry of ferritin into lysosomes and a cytosolic route in which iron is extracted from ferritin prior to degradation by the proteosome.

Parkinsonian Motor Deficits Are Reflected by Proportional A9/A10 Dopamine Neuron Degeneration in the Rat

2001 ◽  
Vol 172 (2) ◽  
pp. 363-376 ◽  
Author(s):  
A.E. Moore ◽  
F. Cicchetti ◽  
J. Hennen ◽  
O. Isacson
Keyword(s):  
Dopamine Neuron ◽  
Motor Deficits ◽  
Neuron Degeneration

Genetic iron chelation protects against proteasome inhibition-induced dopamine neuron degeneration

2010 ◽  
Vol 37 (2) ◽  
pp. 307-313 ◽  
Author(s):  
Wen Zhu ◽  
Xuping Li ◽  
Wenjie Xie ◽  
Feifei Luo ◽  
Deepinder Kaur ◽  
...  
Keyword(s):  
Iron Chelation ◽  
Proteasome Inhibition ◽  
Dopamine Neuron ◽  
Neuron Degeneration
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