Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Jiang, Hong; Song, Ning; Xu, Huamin; Zhang, Shuzhen; Wang, Jun; Xie, Junxia

doi:10.1038/cr.2010.20

Cited by 114 publications

(101 citation statements)

References 44 publications

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“…VPS35 is also responsible for divalent metal transporter 1 transport [224]. Mutated VPS35 may, therefore, lead to divalent metal transporter 1 missorting and iron accumulation, similar to the iron accumulation described in PD patients and in the 6-OHDA mouse model of PD [225]. Finally, VPS35 is also hypothesized to influence the Wnt signaling pathway via deficient sorting of the Wntless protein, which leads to Wntless degradation [226][227][228] and Wnt/b-catenin signaling is impaired in 6-OHDA-lesioned rats [229] and MPTP-induced mouse and monkey models [230].…”

Section: Vps35 (Park17)mentioning

confidence: 84%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to a variety of motor and non-motor symptoms. Interestingly, nonmotor symptoms often appear a decade or more before the first signs of motor symptoms. Some of these non-motor symptoms are remarkably similar to those observed in cases of impaired neurogenesis and several PD-related genes have been shown to play a role in embryonic or adult neurogenesis. Indeed, animal models deficient in Nurr1, Pitx3, SNCA and PINK1 display deregulated embryonic neurogenesis and LRRK2 and VPS35 have been implicated in neuronal development-related processes such as Wnt/bcatenin signaling and neurite outgrowth. Moreover, adult neurogenesis is affected in both PD patients and PD animal models and is regulated by dopamine and dopaminergic (DA) receptors, by chronic neuroinflammation, such as that observed in PD, and by differential expression of wild-type or mutant forms of PD-related genes. Indeed, an increasing number of in vivo studies demonstrate a role for SNCA and LRRK2 in adult neurogenesis and in the generation and maintenance of DA neurons. Finally, the roles of PDrelated genes, SNCA, LRRK2, VPS35, Parkin, PINK1 and DJ-1 have been studied in NSCs, progenitor cells and induced pluripotent stem cells, demonstrating a role for some of these genes in stem/progenitor cell proliferation and maintenance. Together, these studies strongly suggest a link between deregulated neurogenesis and the onset and progression of PD and present strong evidence that, in addition to a neurodegenerative disorder, PD can also be regarded as a developmental disorder.

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Section: Vps35 (Park17)mentioning

confidence: 84%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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“…Our previous studies showing that DMT11IRE downregulation could be initiated by IRP1 knockdown may further confirm this notion. 8 Abnormal cerebral perfusion occurs in PD. 9 Hypoxia and other factors have been reported to suppress IRP/IRE binding affinity and to induce the downregulation of IRPs.…”

Section: Resultsmentioning

confidence: 99%

Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease

Song

et al. 2013

Neurology

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Objective: The present study aimed to evaluate alterations in the levels of iron, divalent metal transporter 1 (DMT1) with the iron-responsive element (IRE), transferrin receptor 1 (TfR1), ferroportin 1 (FPN1), and iron regulatory protein 1 (IRP1) in the temporal cortex of human brains with Parkinson disease (PD).Methods: Iron content was measured using an ICP-MS 7500CE detector. IRP1, DMT11IRE, TfR1, and FPN1 expressions were determined by Western blotting.Results: Iron content was significantly lower in the temporal cortex of patients with PD when compared with age-matched healthy controls. Unexpectedly, the levels of DMT11IRE, TfR1, FPN1, and IRP1 were decreased in the temporal cortex in PD brains. No changes were observed in the temporal cortex of postmortem Alzheimer disease brains.Conclusions: Iron deprivation and iron-related protein dysregulation suggest that a different iron regulatory mechanism may exist, and that iron redistribution may occur between the temporal cortex and the substantia nigra of patients with PD. Neurology Postmortem studies have demonstrated that iron selectively accumulates in the substantia nigra (SN) of patients with Parkinson disease (PD).1 The dysregulation of iron transporters is thought to contribute to iron deposition in PD. Recently, increased expression of the iron importer divalent metal transporter 1 (DMT1) with the iron-responsive element (IRE, DMT1+IRE) has been reported in the SN of postmortem PD brains.2 Meanwhile, the downregulation of ferroportin 1 (FPN1), an iron exporter, was also suggested to be related to 6-hydroxydopamineinduced nigral iron accumulation. 3 However, it is unknown whether iron metabolism is disrupted in brain regions other than the SN (e.g., the cerebral cortex) and how this occurs. In this study, we investigated iron content in the temporal cortex of postmortem PD brains. Unexpectedly, we observed decreased iron content in this brain region in PD but not in Alzheimer disease (AD). To investigate the underlying mechanism, we further evaluated alterations in transporter expression, particularly DMT11IRE, FPN1, and transferrin receptor 1 (TfR1). In PD brains, we observed decreased protein levels of DMT11IRE, FPN1, and TfR1, and decreased expression of iron regulatory protein 1 (IRP1) in the cortex. These results imply that a different iron regulatory mechanism may exist in the temporal cortex, and that iron redistribution might occur between the cortex and SN in PD.METHODS Subjects. The patients were recruited from Sun City, Arizona, a major suburb of Phoenix with a population of approximately 70

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“…In addition, it has been reported that RA could protect MES23.5 dopaminergic cells against 6-OHDA- [105] or MPP + [106] -induced neurotoxicity in vitro and achieve neurorescue effects in 6-ODHA-lesioned rat model of PD in vivo [107] . (2) RA has an early renal protective role in nephritic damage.…”

Section: Other Pharmacological Findingsmentioning

confidence: 99%

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

Wang

2012

Acta Pharmacol Sin

108

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Salvia miltiorrhiza, a traditional medical herb known as danshen, has been widely used in China to improve blood circulation, relieve blood stasis, and treat coronary heart disease. S miltiorrhiza depside salt is a novel drug recently developed at the Shanghai Institute of Materia Medica; it contains magnesium lithospermate B (MLB) and its analogs, rosmarinic acid (RA) and lithospermic acid (LA), as active components. The drug has been used in the clinic to improve blood circulation and treat coronary heart disease. The pharmacological effects of the depside salt from S miltiorrhiza and its components have been extensively investigated. Experimental studies have demonstrated that magnesium lithospermate B possesses a variety of biological activities, especially protective effects in the cardiovascular system such as attenuation of atherosclerosis and protection against myocardial ischemia-reperfusion injury. Rosmarinic acid and lithospermic acid also show beneficial effects on the cardiovascular system. This paper reviews the recent findings regarding the mechanisms underlying the pharmacological actions of the active components of S miltiorrhiza depside salt, based on published works and our own observations.

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Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Cited by 114 publications

References 44 publications

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease

Pharmacological actions and therapeutic applications of Salvia miltiorrhiza depside salt and its active components

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