Abstract:
:Amyotrophic Lateral Sclerosis is a devastating neurological disease that is inevitably fatal after 3-5years duration. Treatment options are minimal and as such new therapeutic modalities are required. In this review, we discuss the role of the myostatin pathway as a modulator of skeletal muscle mass and therapeutic approaches using biological based therapies. Both monoclonal antibodies to myostatin and a soluble receptor decoy to its high affinity receptor have been used in clinical trials of neuromuscular diseases and while there have been efficacy signals with the latter approach there have also been safety issues. Our approach is to target the high affinity receptor-binding site on myostatin and to develop a next generation set of therapeutic reagents built on a novel protein scaffold. This is the natural single domain VNAR found in sharks which is extremely versatile and has the ability to develop products with superior properties compared to existing therapeutics.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Walsh FS,Rutkowski JLdoi
10.1016/j.neuint.2012.07.016subject
Has Abstractpub_date
2012-11-01 00:00:00pages
931-5issue
6eissn
0197-0186issn
1872-9754pii
S0197-0186(12)00236-7journal_volume
61pub_type
杂志文章,评审abstract::For elucidation of thyroid hormone-induced responsiveness of fish brain, various doses (0.012, 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2 and 4 ?g/g) of triiodothyronine (T(3)) were injected in Singi fish, Heteropneustes fossilis (Bloch), for 3 consecutive days and the changes in cytosolic NADP-dependent malic enzyme (ME, EC 1...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(89)90036-3
更新日期:1989-01-01 00:00:00
abstract::Exposure to high levels of manganese (Mn) results in a neurological disorder, termed manganism, which shares a similar phenotype to Parkinson's disease due to the involvement of the basal ganglia circuitry in both. The initial symptoms of manganism are likely due to the involvement of the globus pallidus, a region ric...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2005.10.012
更新日期:2006-05-01 00:00:00
abstract::Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxal-5'-phosphate (PLP)-dependent biosynthesis of taurin...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2015.08.013
更新日期:2015-11-01 00:00:00
abstract::The effect of the N-methylisoquinolinium ion (NMIQ(+)) on the activity of enzymes related to metabolism of dopamine was studied using a rat clonal pheochromocytoma PC12h cell line. The activities of tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were inhibited by NMIQ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(89)90138-1
更新日期:1989-01-01 00:00:00
abstract::Primary cultures of cerebral cortical astrocytes and neurons, as well as neurons growing on top of the astrocytes (sandwich co-cultures), were incubated with 1-[13C]glucose or 2-[13C]acetate and in the presence or absence of the glutamine synthetase inhibitor methionine sulfoximine. [13C]NMR spectroscopy at 125 MHz wa...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(93)90064-c
更新日期:1993-01-01 00:00:00
abstract::In this paper, two different aspects of growth hormone neuroregulation during aging were considered. Twenty-month-old male rats had decreased growth hormone-releasing hormone mRNA levels and a slight reduction of somatostatin mRNA levels in the hypothalamus when compared to 8-month-old counterparts. Short-term adminis...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(94)90045-0
更新日期:1994-07-01 00:00:00
abstract::Depression is characterized by sadness, purposelessness, irritability, and impaired body functions. Depression causes severe symptoms for several weeks, and dysthymia, which may cause chronic, low-grade symptoms. Treatment of depression involves psychotherapy, medications, or phototherapy. Clinical and experimental ev...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2012.12.014
更新日期:2013-02-01 00:00:00
abstract::Alpha-synuclein (ASN), a 140-amino acid protein, is richly expressed in presynaptic terminals in the central nervous system, where it plays a role in synaptic vesicle function. However, if it is altered and accumulated it is involved in neurodegeneration as Parkinson's disease (PD). ASN contained 35-amino acid domain ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.01.025
更新日期:2006-09-01 00:00:00
abstract::Transport activity of d-pipecolic acid and of l-pipecolic acid in mouse brain and peripheral tissues were tested, and the effect of immobilization stress was described, along with the method for preparative, enantiomeric resolution and purification of d,l-pipecolic acid using high performance liquid chromatography equ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(88)90057-5
更新日期:1988-01-01 00:00:00
abstract::Rapid administration of large doses of ammonia leads to death of animals, which is largely prevented by pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists. The present study focuses on a subunit(s) of NMDA receptor involved in ammonia-induced death by use of NMDA receptor GluRepsilon subunit-deficient ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(03)00124-4
更新日期:2004-01-01 00:00:00
abstract::The consequences of irreversibly-inhibiting D2 dopaminergic receptors on the expression of D1 and D2 dopamine receptor mRNAs and proenkephalin mRNA and on the levels of mu- and delta-opioid receptors in rat striatum were studied following single or repeated administration of the irreversibly-acting D2 dopamine recepto...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(94)90143-0
更新日期:1994-10-01 00:00:00
abstract::Neural stem (NS) cells are multipotent cells defined by their capacity to proliferate and differentiate into all neuronal and glial phenotypes. NS cells can be obtained from specific regions of the adult brain, or generated from embryonic stem cells (ESCs). NS cells differentiate into neural progenitor (NP) cells and ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2011.04.002
更新日期:2011-09-01 00:00:00
abstract::We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performa...
journal_title:Neurochemistry international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.neuint.2017.05.010
更新日期:2017-09-01 00:00:00
abstract::The GLS1 gene encodes a mitochondrial glutaminase that is highly expressed in brain, kidney, small intestine and many transformed cells. Recent studies have identified multiple lysine residues in glutaminase that are sites of N-acetylation. Interestingly, these sites are located within either a loop segment that regul...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2014.12.003
更新日期:2015-09-01 00:00:00
abstract::ATPase activities in CNS membranes were studied after administration of desipramine (DMI), a noradrenaline (NA) uptake inhibitor. In a previous paper we reported that Na+,K(+)-ATPase activity significantly increased 3 h after DMI administration (10 mg/kg) in hypothalamus and mesencephalus but not in cerebral cortex an...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(94)90133-3
更新日期:1994-01-01 00:00:00
abstract::Two puromycin-sensitive aminopeptidase isozymes (PSA-I and PSA-II) were isolated from chicken brain cytosol by ammonium sulfate fractionation followed by column chromatography on Cellex D and AH-Sepharose 4B and separated on Bio-Gel HTP. Each was purified to homogeneity on Sephadex G-200, Arg-Tyr-AH-Sepharose, Bio-Gel...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(93)90039-8
更新日期:1993-05-01 00:00:00
abstract::Age is the leading risk factor for many of the most prevalent and devastating diseases including neurodegenerative diseases. A number of herbal medicines have been used for centuries to ameliorate the deleterious effects of ageing-related diseases and increase longevity. Oxidative stress is believed to play a role in ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2012.08.018
更新日期:2013-04-01 00:00:00
abstract::The labelling of gangliosides and sialoglycoproteins (SGP) after injecting intraocularly 30 ?Ci of [(3)H]ManNAc was studied in chickens that had previously received, also intraocularly, 30 or 70 nmol of monensin in 10 ?l of ethanol or 24 ?g of colchicine in 10 ?l saline. Controls received ethanol or saline only. Colch...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(86)90183-x
更新日期:1986-01-01 00:00:00
abstract::The present study has been designed to establish the potential benefits from 1-methylnicotinamide (MNA) treatment on brain disorders associated with type 1 diabetes. All experiments were carried out after 6 weeks of streptozotocin-induced diabetes (60 mg/kg of body weight, i.p.) in male Wistar rats treated for 5 weeks...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2009.10.004
更新日期:2010-01-01 00:00:00
abstract::The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorp...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(00)00106-6
更新日期:2001-04-01 00:00:00
abstract::There has arisen considerable interest in the study of dopamine D(2/3) agonist binding sites by positron emission tomography (PET), based on the claim that agonist sites represent a functional subset of the total number of sites labeled by more conventional antagonist ligands. To test the basis of this claim, we used ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2010.01.010
更新日期:2010-05-01 00:00:00
abstract::A simple procedure for isolating a fraction enriched in synaptic plasma membrane (SPM) vesicles from sheep brain cortex is described and is used in studying uptake and release of [(3)H]GABA. The crude synaptosomal fraction was subjected to osmotic shock and the lysate was subfractioned in a discontinuous density gradi...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(90)90022-l
更新日期:1990-01-01 00:00:00
abstract::It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic n...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2012.05.022
更新日期:2012-11-01 00:00:00
abstract::In order to compare the incorporation of several saturated fatty acids into the brain, radioactive palmitic, stearic and lignoceric acids were injected into mice. The radioactivity was measured in lipids from isolated neurons, astrocytes and myelin. Our data indicate that specific radioactivity of lignoceric acid afte...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(81)90020-6
更新日期:1981-01-01 00:00:00
abstract::A decrease in the osmolarity of incubation medium is accompanied by calcium influx in neuronal presynaptic endings. We studied the influence of Ca2+ on exocytosis induced by hypotonic shock using the hydrophilic fluorescent dye acridine orange and the hydrophobic fluorescent dye FM2-10. It was shown using acridine ora...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2004.09.002
更新日期:2005-02-01 00:00:00
abstract::Essential metals are crucial for the maintenance of cell homeostasis. Among the 23 elements that have known physiological functions in humans, 12 are metals, including iron (Fe) and manganese (Mn). Nevertheless, excessive exposure to these metals may lead to pathological conditions, including neurodegeneration. Simila...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2012.12.006
更新日期:2013-04-01 00:00:00
abstract::The roles of membrane depolarization and calcium influx in the regulation of retinal serotonin N-acetyltransferase (NAT) activity were investigated in low-density monolayer cultures of chick retinal cells, in which photoreceptors represented approximately 70% of the total cell population. NAT activity expressed by the...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(90)90075-5
更新日期:1990-01-01 00:00:00
abstract::Gastrointestinal peptides and hormones are known to penetrate through the utero-placental barrier and regulate fetal development. In the present study, we tested permeation of maternal brain-derived neurotrophic factor (BDNF) to fetuses, using BDNF-gene deficient mice and exogenous BDNF administration. At embryonic da...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.11.005
更新日期:2009-02-01 00:00:00
abstract::Poly(ADP-ribose)polymerase-1 (PARP-1) overactivation is a key event in neurodegeneration but the underlying molecular mechanisms wait to be unequivocally identified. Energy failure, transcriptional derangement and deadly nucleus-mitochondria cross-talk have been proposed as mechanisms responsible for PARP-1 neurotoxic...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.08.009
更新日期:2007-01-01 00:00:00
abstract::Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H₂O₂). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this stud...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2012.02.004
更新日期:2012-04-01 00:00:00