Intracellular iron concentration of neurons with and without perineuronal nets

Fiedler, Anja; Reinert, Tilo; Morawski, Markus; Brückner, Gert; Arendt, Thomas; Butz, T.

doi:10.1016/j.nimb.2007.02.069

Cited by 40 publications

(35 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As it is well established that Fenton chemistry can play a critical role in deleterious oxidative stress (Kohen and Nyska, 2002; Prousek, 2007; Thomas et al, 2009), and these compounds are neuroprotective at the approximate concentration of free chelatable cellular iron (Fiedler et al, 2007), we reasoned that the metal chelating property of these hydroxamic acids is crucially important for protecting neurons from a H 2 O 2 insult. To test this hypothesis, we measured the ability of each of these compounds to bind iron using an in vitro calcein assay (Figure 3) and found that several of them could bind metals in cells (Figure S2A) (Cabantchik et al, 1996).…”

Section: Resultsmentioning

confidence: 99%

Hydroxamate-Based Histone Deacetylase Inhibitors Can Protect Neurons from Oxidative Stress via a Histone Deacetylase-Independent Catalase-Like Mechanism

Olson

Bourassa

Wagner

et al. 2015

Chemistry & Biology

View full text Add to dashboard Cite

Summary Histone deacetylase (HDAC) inhibitors have shown enormous promise for treating various disease states, presumably due to their ability to modulate acetylation of histone and non-histone proteins. Many of these inhibitors contain functional groups capable of strongly chelating metal ions. We demonstrate that several members of one such class of compounds, the hydroxamate-based HDAC inhibitors, can protect neurons from oxidative stress via an HDAC-independent mechanism. This previously unappreciated antioxidant mechanism involves the in situ formation of hydroxamate-iron complexes that catalyze the decomposition of hydrogen peroxide in a manner reminiscent of catalase. We demonstrate that while many hydroxamate-containing HDAC inhibitors display a propensity for binding iron, only a subset form active catalase mimetics capable of protecting neurons from exogenous H2O2. In addition to impacting stroke and neurodegenerative disease research, these results highlight the possibility that HDAC-independent factors might play a role in the therapeutic effects of hydroxamate-based HDAC inhibitors.

show abstract

Section: Resultsmentioning

confidence: 99%

Hydroxamate-Based Histone Deacetylase Inhibitors Can Protect Neurons from Oxidative Stress via a Histone Deacetylase-Independent Catalase-Like Mechanism

Olson

Bourassa

Wagner

et al. 2015

Chemistry & Biology

View full text Add to dashboard Cite

show abstract

“…The total Fe complement of a neuron is within the lM range (Fiedler et al 2007). It is estimated that the reactive labile iron pool (LIP) represents < 5% of total cellular Fe in a redox-active and chelatable state (Kakhlon and Cabantchik 2002).…”

Section: Discussionmentioning

confidence: 99%

l‐3,4‐dihydroxyphenylalanine (l‐DOPA) modulates brain iron, dopaminergic neurodegeneration and motor dysfunction in iron overload and mutant alpha‐synuclein mouse models of Parkinson's disease

Billings

Gordon

Rawling

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Treatment with the dopamine (DA) precursor l‐3,4‐dihydroxyphenylalanine (l‐DOPA) provides symptomatic relief arising from DA denervation in Parkinson's disease. Mounting evidence that DA autooxidation to neurotoxic quinones is involved in Parkinson's disease pathogenesis has raised concern about potentiation of oxidative stress by l‐DOPA. The rate of DA quinone formation increases in the presence of excess redox‐active iron (Fe), which is a pathological hallmark of Parkinson's disease. Conversely, l‐DOPA has pH‐dependent Fe‐chelating properties, and may act to ‘redox silence’ Fe and partially allay DA autoxidation. We examined the effects of l‐DOPA in three murine models of parkinsonian neurodegeneration: early‐life Fe overexposure in wild‐type mice, transgenic human (h)A53T mutant α‐synuclein (α‐syn) over‐expression, and a combined ‘multi‐hit’ model of Fe‐overload in hA53T mice. We found that l‐DOPA was neuroprotective and prevented age‐related Fe accumulation in the substantia nigra pars compacta (SNc), similar to the mild‐affinity Fe chelator clioquinol. Chronic l‐DOPA treatment showed no evidence of increased oxidative stress in wild‐type midbrain and normalized motor performance, when excess Fe was present. Similarly, l‐DOPA also did not exacerbate protein oxidation levels in hA53T mice, with or without excess nigral Fe, and showed evidence of neuroprotection. The effects of l‐DOPA in Fe‐fed hA53T mice were somewhat muted, suggesting that Fe‐chelation alone is insufficient to attenuate neuron loss in an animal model also recapitulating altered DA metabolism. In summary, we found no evidence in any of our model systems that l‐DOPA treatment accentuated neurodegeneration, suggesting DA replacement therapy does not contribute to oxidative stress in the Parkinson's disease brain.

show abstract

“… X-ray Fluorescence Spectrometry (XRF) or Rapid Scan X-ray fluorescence spectrometry (RS-XRF) [ 71 , 72 ]: This technique allows for iron mapping and experiments have been conducted at two different locations; at the Stanford Synchrotron radiation laboratories (SSRL) [ 73 ] or more recently at the new Diamond light source in Oxfordshire, UK [ 74 ]. Proton-Induced X-ray Emission (PIXE) [ 75 , 76 , 77 ]: A similar principle as XRF allowing to create iron maps of brain tissue [ 78 , 79 , 80 ]. …”

Section: Iron Detection Methodsmentioning

confidence: 99%

Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping

Stüber

Pitt

Wang

2016

IJMS

View full text Add to dashboard Cite

Iron is considered to play a key role in the development and progression of Multiple Sclerosis (MS). In particular, iron that accumulates in myeloid cells after the blood-brain barrier (BBB) seals may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration. Magnetic resonance imaging (MRI) is a well-established tool for the non-invasive study of MS. In recent years, an advanced MRI method, quantitative susceptibility mapping (QSM), has made it possible to study brain iron through in vivo imaging. Moreover, immunohistochemical investigations have helped defining the lesional and cellular distribution of iron in MS brain tissue. Imaging studies in MS patients and of brain tissue combined with histological studies have provided important insights into the role of iron in inflammation and neurodegeneration in MS.

show abstract

Intracellular iron concentration of neurons with and without perineuronal nets

Cited by 40 publications

References 27 publications

Hydroxamate-Based Histone Deacetylase Inhibitors Can Protect Neurons from Oxidative Stress via a Histone Deacetylase-Independent Catalase-Like Mechanism

Hydroxamate-Based Histone Deacetylase Inhibitors Can Protect Neurons from Oxidative Stress via a Histone Deacetylase-Independent Catalase-Like Mechanism

l‐3,4‐dihydroxyphenylalanine (l‐DOPA) modulates brain iron, dopaminergic neurodegeneration and motor dysfunction in iron overload and mutant alpha‐synuclein mouse models of Parkinson's disease

Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping

Contact Info

Product

Resources

About