Abstract:
:Brain iron homeostasis is increasingly recognized as a potential target for the development of drug therapies for aging-related disorders. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. Indeed, many proteins initially characterized in those diseases such as amyloid-β protein, α-synuclein, and huntingtin have been linked to iron neurochemistry. Iron plays a crucial role in maintaining normal physiological functions in the brain through its participation in many cellular functions such as mitochondrial respiration, myelin synthesis, and neurotransmitter synthesis and metabolism. However, excess iron is a potent source of oxidative damage through radical formation and because of the lack of a body-wide export system, a tight regulation of its uptake, transport and storage is crucial in fulfilling cellular functions while keeping its level below the toxicity threshold. In this review, we discuss the current knowledge on iron homeostasis in the brain and explore how alterations in brain iron metabolism affect neuronal function with emphasis on iron dysregulation in Alzheimer's and Parkinson's diseases. Finally, we discuss recent findings implicating iron as a diagnostic and therapeutic target for Alzheimer's and Parkinson's diseases. Iron plays a fundamental role in maintaining the high metabolic and energetic requirements of the brain. However, iron has to be maintained in a delicate balance as both iron overload and iron deficiency are detrimental to the brain and can trigger neurodegeneration. Here, we discuss the current knowledge on brain iron homeostasis and its involvement in major aging-related neurodegenerative diseases. This article is part of a special issue on Parkinson disease.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Belaidi AA,Bush AIdoi
10.1111/jnc.13425subject
Has Abstractpub_date
2016-10-01 00:00:00pages
179-197eissn
0022-3042issn
1471-4159journal_volume
139 Suppl 1pub_type
杂志文章,评审abstract::We have analyzed brain coated vesicles and synaptic plasma membrane for the presence of the plasma membrane proteolipid protein. Coated vesicles were isolated from calf brain gray matter with a final purification on Sephacryl S-1000 and reisolated twice by chromatography to ensure homogeneity. Fractions were analyzed ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb01829.x
更新日期:1988-09-01 00:00:00
abstract::Calcium-activated neutral proteases (calpains) are regulated by specific endogenous protein inhibitors, the calpastatins, which are widely distributed in mammalian tissues. Calpastatins from different species or in various tissues from the same species exhibit considerable size heterogeneity on sodium dodecyl sulfate ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64020859.x
更新日期:1995-02-01 00:00:00
abstract::The antisense strategy was used to unravel the functional contribution of the mRNAs encoding dopamine (DA) receptors to the multiple transduction mechanisms operated by DA in rat pituitary cells. An antisense oligonucleotide was designed to recognize seven nucleotides upstream and 11 nucleotides downstream from the in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62041260.x
更新日期:1994-04-01 00:00:00
abstract::We investigated the mechanism of increases in cyclic GMP levels in bovine superior cervical ganglion (SCG) in response to muscarinic receptor stimulation. Acetylcholine increased cyclic GMP levels in SCG. This increase was inhibited by NG-methyl-L-arginine (NMA), and the inhibition was reversed by L-arginine. Soluble ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb03628.x
更新日期:1993-09-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disease resulting in progressive cognitive decline. Amyloid plaque deposits consisting specifically of beta-amyloid peptides that have formed fibrils displaying beta-pleated sheet conformation are associated with activated microglia and astrocytes, are colocalized with C...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05558.x
更新日期:2008-09-01 00:00:00
abstract::Inducible expression of the group-I metabotropic glutamate receptor (mGlu1alpha) in Chinese hamster ovary cells allows for the study of receptor density dependent effects. However, expression levels attainable with this system are lower than those reported for various brain regions and achieved by conventional (consti...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00405.x
更新日期:2001-06-01 00:00:00
abstract::Abstract Dorfin is a RING-finger type ubiquitin ligase for mutant superoxide dismutase 1 (SOD1) that enhances its degradation. Mutant SOD1s cause familial amyotrophic lateral sclerosis (FALS) through the gain of unelucidated toxic properties. We previously showed that the accumulation of mutant SOD1 in the mitochondri...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2003.02289.x
更新日期:2004-04-01 00:00:00
abstract::Substantial amounts of phospholipase A2 activity were detected in bovine brain cytosol. The major phospholipase A2 activity was present in the precipitate at 40% saturation with solid ammonium sulfate. After the desaltate of the precipitate was loaded onto an Ultrogel AcA 54 gel filtration column, almost all the activ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb09426.x
更新日期:1992-08-01 00:00:00
abstract::Accumulations of the neuropeptides substance P (SP), somatostatin (ST), and vasoactive intestinal polypeptide (VIP) proximal to a crush in the cervical vagus nerve of the rat have been measured using sensitive radioimmunoassays. Each of the peptides was rapidly transport towards the peripheral terminals of vagal affer...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1980.tb04627.x
更新日期:1980-01-01 00:00:00
abstract::The NMDA receptor/channel has been shown to be inhibited by ethanol in the clinically relevant range 25-100 mM. We studied heteromeric assemblies (NR1b/NR2) of the NMDA receptor, expressed in oocytes, to address three questions regarding this inhibition, and discovered the following: (1) The inhibition was nearly equi...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.65010140.x
更新日期:1995-07-01 00:00:00
abstract::We recently described a new protein associated exclusively with neuronal clathrin-coated vesicles (CCVs), and characterized two monoclonal antibodies that react with it (S-8G8 and S-6G7). In this report, the association of neuronal protein of 185 kilodaltons (NP185) with CCV kinases and its interaction with tubulin ar...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb10929.x
更新日期:1989-01-01 00:00:00
abstract::3 alpha-Hydroxysteroid oxidoreductase (EC 1.1.1.50) was localized in the rat brain by cryostat sectioning, microassay, and neurochemical lesions. Single 16-microns sections were cut, homogenized, and assayed. In the olfactory tubercle 3 alpha-hydroxysteroid oxidoreductase activity is high in the piaglial layer at the ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1989.tb07269.x
更新日期:1989-06-01 00:00:00
abstract::The olfactory bulb is one of the most vulnerable brain regions in age-related proteinopathies. Proteinopathic stress is mitigated by the heat shock protein (Hsp) family of chaperones. Here, we describe age-related decreases in Hsc70 in the olfactory bulb of the female rat and higher levels of Hsp70 and Hsp25 in middle...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13041
更新日期:2015-06-01 00:00:00
abstract::The protein B-50 is dephosphorylated in rat cortical synaptic plasma membranes (SPM) by protein phosphatase type 1 and 2A (PP-1 and PP-2A)-like activities. The present studies further demonstrate that B-50 is dephosphorylated not only by a spontaneously active PP-1-like enzyme, but also by a latent form after pretreat...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb08913.x
更新日期:1992-07-01 00:00:00
abstract::: The amyloid cascade hypothesis of Alzheimer's disease envisages that the initial elevation of amyloid β-peptide (Aβ) levels, especially of Aβ(1-42) , is the primary trigger for the neuronal cell death specific to onset of Alzheimer's disease. There is now substantial evidence that brain amyloid levels are manipulabl...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2011.07510.x
更新日期:2012-01-01 00:00:00
abstract::The levels of hexokinase, as well as those of the cytoplasmic glycolytic enzyme lactate dehydrogenase and the mitochondrial tricarboxylic acid cycle enzymes fumarase and citrate synthase, have been determined in whole rat brain and in neuronal, astrocytic, and oligodendroglial fractions isolated from rat brain. Compar...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb08111.x
更新日期:1983-04-01 00:00:00
abstract::Intact neurofilaments (NF) purified from mammalian brain and spinal cord promote the assembly of microtubules in solutions of pure phosphocellulose (PC)-purified tubulin. This assembly is temperature-dependent and is inhibited by mitotic spindle inhibitors. The ability of NF to induce microtubule formation is 20% of t...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb05398.x
更新日期:1984-11-01 00:00:00
abstract::Tau, a microtubule-associated protein, is encoded by a single gene, whose expression is primarily neuronal. In this work, we defined an 80-bp region of the tau promoter that confers tau protein with neuronal expression. This fragment works in conjunction with an endogenous initiation region to activate neuronal precur...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2000.0751408.x
更新日期:2000-10-01 00:00:00
abstract::Unilateral ligation of the left common carotid artery in anesthetized Mongolian gerbils resulted in a steep rise in extracellular dopamine in the ipsilateral striatum in 9 out of 19 animals. Extracellular dopamine was measured by cerebral dialysis in vivo and reached a peak of 0.19 mM at 40 min. At the same time, the ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1988.tb02468.x
更新日期:1988-06-01 00:00:00
abstract::Neural cell adhesion molecule (NCAM) contributes to axon growth and guidance during development and learning and memory in adulthood. Although the Ig domains mediate homophilic binding, outgrowth activity localizes to two membrane proximal fibronectin-like domains. The first of these contains a site identified as a po...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03417.x
更新日期:2005-10-01 00:00:00
abstract::The human brain endothelial capillary cell line hCMEC/D3 has been developed recently as a model for the human blood-brain barrier. In this study a further characterization of this model was performed with special emphasis on permeability properties and active drug transport. Para- or transcellular permeabilities (P(e)...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05730.x
更新日期:2008-12-01 00:00:00
abstract::Ala and Gly substitutions for Pro 101 (P101) located in transmembrane domain 2 of the dopamine transporter (DAT) abolished transport activity but did not disrupt plasma membrane expression. Due to the high conservation of P101 in all neurotransmitter transporters and the capability of Pro to add flexibility to helices...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03196.x
更新日期:2005-07-01 00:00:00
abstract::The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, a...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1984.tb02792.x
更新日期:1984-05-01 00:00:00
abstract::Rat-1 fibroblasts were transduced to express Drosophila choline acetyltransferase. The presence of an active enzyme in these cells (Rat-1/dChAT) was confirmed using various methods. Rat-1/dChAT fibroblasts released acetylcholine (ACh) into the culture medium. Moreover, intra- and extracellular levels of ACh could be i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1992.tb10942.x
更新日期:1992-06-01 00:00:00
abstract::Intrastriatal microdialysis was used to administer muscarinic drugs in freely moving rats for 40 min at a flow rate of 2 microl/min. Administration of the nonselective agonist pilocarpine at 10 mM increased striatal dopamine release and decreased extracellular GABA and glutamate overflow. Perfusion with the muscarinic...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68051942.x
更新日期:1997-05-01 00:00:00
abstract::The efficacy of funnel-freezing of rat brain to inactivate metabolic processes and preserve in vivo tissue glucose concentration was validated by comparing the results obtained by funnel-freezing with those obtained with freeze-blowing of brain. The arterial plasma glucose level was clamped at 9 mM in halothane-anesth...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb02066.x
更新日期:1991-05-01 00:00:00
abstract::Our laboratory demonstrated previously that PGE2-induced modulation of hippocampal synaptic transmission is via a pre-synaptic PGE2 EP2 receptor. However, little is known about whether the EP2 receptor is involved in hippocampal long-term synaptic plasticity and cognitive function. Here we show that long-term potentia...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05766.x
更新日期:2009-01-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) and tissue plasminogen activator (tPA) play important roles in neuronal migration and survival. However, a direct link between the neurotrophic effects of PACAP and tPA has never been investigated. In this study, we show that, in PC12 cells, PACAP induced a 9....
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07486.x
更新日期:2011-12-01 00:00:00
abstract::It has been suggested that release of cytochrome c (Cyt c) from mitochondria during apoptotic death is through opening of the mitochondrial permeability transition pore followed by swelling-induced rupture of the mitochondrial outer membrane. However, this remains controversial and may vary with cell type and model sy...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2002.01049.x
更新日期:2002-09-01 00:00:00
abstract::Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels we...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64062607.x
更新日期:1995-06-01 00:00:00