当前位置： SCI文献检索 > EXPERIMENTAL NEUROLOGY期刊下所有文献 > Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.

Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.

Abstract：

:Downregulation in the astroglial glutamate transporter EAAT2 in amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 mouse models of ALS is believed to contribute to the death of motor neurons by excitotoxicity. We previously reported that caspase-3 cleaves EAAT2 at a unique cleavage consensus site located in its c-terminus domain, a proteolytic cleavage that also occurs in vivo in the mutant SOD1 mouse model of ALS and leads to accumulation of a sumoylated EAAT2 C-terminus fragment (CTE-SUMO1) beginning around onset of disease. CTE-SUMO1 accumulates in PML nuclear bodies of astrocytes and causes them to alter their mature phenotypes and secrete factors toxic to motor neurons. Here, we report that mutating the caspase-3 consensus site in the EAAT2 sequence with an aspartate to asparagine mutation (D504N), thereby inhibiting caspase-3 cleavage of EAAT2, confers protection to the SOD1-G93A mouse. EAAT2-D504N knock-in mutant mice were generated and crossed with SOD1-G93A mice to assess the in vivo pathogenic relevance for ALS symptoms of EAAT2 cleavage. The mutation did not affect normal EAAT2 function nor non-ALS mice. In agreement with the timing of CTE-SUMO1 accumulation, while onset of disease was not affected, the mutation caused an extension in progression time, a delay in the development of hindlimb and forelimb muscle weakness, and a significant increase in the lifespan of SOD1-G93A mice.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Rosenblum LT,Shamamandri-Markandaiah S,Ghosh B,Foran E,Lepore AC,Pasinelli P,Trotti D

doi

10.1016/j.expneurol.2017.03.014

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

145-153

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(17)30074-2

journal_volume

292

pub_type

杂志文章

相关文献

EXPERIMENTAL NEUROLOGY文献大全
  • Differential responses to methylmercury exposure and recovery in neuroblastoma and glioma cells and fibroblasts.

    abstract：:The effects of methylmercury (MeHg) on cytoplasmic microtubules in cultured neuroblastoma cells, glioma cells, and fibroblasts were compared. Neuroblastoma cells appeared to be more sensitive to disruption of microtubules by MeHg than the glioma cells or fibroblasts; cellular concentrations of mercury after MeHg were ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(84)90147-x

    authors： Sager PR,Syversen TL

    更新日期：1984-08-01 00:00:00

  • A role for the bilateral involvement of perirhinal cortex in generalized kindled seizure expression.

    abstract：:The perirhinal cortex (PRh) has been suggested as a substrate for the expression of generalized clonic seizures in the late stages of kindling development (stages 4-5). Using the induction of Fos as a marker of neuronal activation, the PRh region was investigated after kindling or nonkindling electrical stimulation. N...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1998.6794

    authors： Ferland RJ,Nierenberg J,Applegate CD

    更新日期：1998-05-01 00:00:00

  • The "campus syndrome" in pigs: neurological, neurophysiological, and neuropharmacological characterization of a new genetic animal model of high-frequency tremor.

    abstract：:Inherited neurological diseases in animals are of interest to a wide range of scientific disciplines, particularly because such animals may be suited as genetic animal models for respective human disorders. Because the pig has a number of anatomic and physiologic features similar to those of human beings, this species...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1995.1050

    authors： Richter A,Wissel J,Harlizius B,Simon D,Schelosky L,Scholz U,Poewe W,Löscher W

    更新日期：1995-08-01 00:00:00

  • Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.

    abstract：:The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy i...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2008.08.013

    authors： Melli G,Taiana M,Camozzi F,Triolo D,Podini P,Quattrini A,Taroni F,Lauria G

    更新日期：2008-12-01 00:00:00

  • Neurotrophic properties of olfactory ensheathing glia.

    abstract：:Olfactory ensheathing cells (OEC) constitute a specialized population of glia that accompany primary olfactory axons and have been reported to facilitate axonal regeneration after spinal cord injury in vivo. In the present report we describe OEC neurotrophic factor expression and neurotrophic properties of OECs in vit...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/s0014-4886(02)00058-4

    authors： Lipson AC,Widenfalk J,Lindqvist E,Ebendal T,Olson L

    更新日期：2003-04-01 00:00:00

  • Neurodegeneration in autoimmune CNS inflammation.

    abstract：:Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, in which the myelin sheath has been considered to be the primary target for many years. However, an increasing number of reports have focused on neurodegenerative aspects of the disease pathogenesis. Recent studies i...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2009.11.019

    authors： Herz J,Zipp F,Siffrin V

    更新日期：2010-09-01 00:00:00

  • Optogenetic exploration and modulation of pain processing.

    abstract：:Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in nociceptive processing in the peripheral and central nervous systems contribute to the onset and maintenance of chronic pain. The past se...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2018.05.003

    authors： Xie YF,Wang J,Bonin RP

    更新日期：2018-08-01 00:00:00

  • Levodopa induction of Fos immunoreactivity in rat brain following partial and complete lesions of the substantia nigra.

    abstract：:It is controversial whether levodopa (L-DOPA) therapy in the early stages of Parkinson's disease (PD) predisposes to later complications. Partial lesions of the substantia nigra (SN) in rat provide a model of the early stages of PD. We have investigated the potential effects of L-DOPA in early PD by analyzing its infl...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1993.1057

    authors： Cole DG,Growdon JH,DiFiglia M

    更新日期：1993-04-01 00:00:00

  • Hereditary peroneal muscular atrophy in the mouse: an experimental model for congenital contractures (arthrogryposis).

    abstract：:A new mutant, peroneal muscular atrophy (pma) mouse in CF#1 strain has an autosomal recessively inherited equinovarus (club foot deformity) of the hind legs because of the absence of the common peroneal nerve branch of the sciatic nerve. We found the peroneal muscles were hypoplastic with histochemical and electron mi...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(86)90053-1

    authors： Nonaka I,Kikuchi A,Suzuki T,Esaki K

    更新日期：1986-03-01 00:00:00

  • Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease.

    abstract：:In vivo imaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. These reductions likely follow regional synaptic loss or d...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1006/exnr.1996.0180

    authors： Chandrasekaran K,Hatanpää K,Brady DR,Rapoport SI

    更新日期：1996-11-01 00:00:00

  • Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors--Recommendations for methods and experimental designs.

    abstract：:Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are cau...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2015.03.010

    authors： Losen M,Martinez-Martinez P,Molenaar PC,Lazaridis K,Tzartos S,Brenner T,Duan RS,Luo J,Lindstrom J,Kusner L

    更新日期：2015-08-01 00:00:00

  • Neurotrophin ligand-receptor systems in somatosensory cortex of adult rat are affected by repeated episodes of ethanol.

    abstract：:Ethanol exposure profoundly affects learning and memory and neural plasticity. Key players underlying these functions are neurotrophins. The present study explored the effects of ethanol on the distribution of neurotrophins in the cerebral cortex of the adult rat. Age- and weight-matched pairs of adult male, Long-Evan...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2006.12.022

    authors： Bruns MB,Miller MW

    更新日期：2007-04-01 00:00:00

  • Role of the corpus callosum and hippocampal commissure on transfer phenomenon in amygdala-kindled cats.

    abstract：:Forebrain-bisected cats underwent kindling at primary and secondary amygdala sites. The behavioral effect of amygdala kindling was then examined according to the extent of the surgical lesion in the forebrain commissures. Bisection of the corpus callosum with or without lesion of the hippocampal commissure modified bo...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(87)90083-5

    authors： Fukuda H,Wada JA,Riche D,Naquet R

    更新日期：1987-10-01 00:00:00

  • Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats.

    abstract：:Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gam...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2014.12.016

    authors： Bian H,Hu Q,Liang X,Chen D,Li B,Tang J,Zhang JH

    更新日期：2015-03-01 00:00:00

  • End-plate growth exceeds nerve terminal growth in juvenile mice.

    abstract：:An electron microscopic investigation of neuromuscular synapses of the tensor fasciae latae muscle in juvenile mice was carried out to determine the relationship between the presynaptic (nerve terminal) and postsynaptic (end-plate plaque) elements during the major phase of postnatal growth. In the first month of life ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(87)90065-3

    authors： Habgood MD,Hopkins WG

    更新日期：1987-05-01 00:00:00

  • Facial nerve regeneration in the silicone chamber: the influence of nerve growth factor.

    abstract：:The role of nerve growth factor (NGF) was examined in the neural repair of adult rabbit facial nerves using an in vivo preparation. A 35-microliters nerve growth chamber was created by suturing the proximal and distal ends of a transected facial nerve (superior buccal branch) into a silicone tube. A gap of 8 mm in the...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(89)90184-2

    authors： Chen YS,Wang-Bennett LT,Coker NJ

    更新日期：1989-01-01 00:00:00

  • Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

    abstract：:In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. ...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2012.01.010

    authors： Timmerman V,Clowes VE,Reid E

    更新日期：2013-08-01 00:00:00

  • An autoradiographic study of delta-aminolevulinic acid uptake by mouse brain.

    abstract：:delta-Aminolevulinic acid (ALA), a toxic precursor of porphyrin, when injected i.v. failed to enter most brain structures, such as the cortex, thalamus, midbrain, and others, as determined by the autoradiographic technique. However, the choroid plexus, median eminence, and a narrow strip of the periventricular zone, w...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(83)90234-0

    authors： Terr L,Weiner LP

    更新日期：1983-02-01 00:00:00

  • Activation of noradrenergic transmission by alpha2-adrenoceptor antagonists counteracts deafferentation-induced neuronal death and cell proliferation in the adult mouse olfactory bulb.

    abstract：:The olfactory bulb is the target of neural progenitor cells that are generated in the subventricular zone of the lateral ventricle in the adult brain. This permanent neurogenesis is likely influenced by olfactory input to the bulb since previous studies have shown that cell proliferation and/or apoptotic death are sti...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2005.03.004

    authors： Veyrac A,Didier A,Colpaert F,Jourdan F,Marien M

    更新日期：2005-08-01 00:00:00

  • Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human neuroblastoma cells.

    abstract：:Alcohol intake is one of the important lifestyle factors for the risk of insulin resistance and type 2 diabetes. Acetaldehyde, the major ethanol metabolite which is far more reactive than ethanol, has been postulated to participate in alcohol-induced tissue injury although its direct impact on insulin signaling is unc...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2006.08.002

    authors： Fang CX,Yang X,Sreejayan N,Ren J

    更新日期：2007-01-01 00:00:00

  • Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis impairs social behavior and cognitive function of adult male offspring.

    abstract：:Vasoactive intestinal peptide (VIP) is a regulator of rodent embryogenesis during the period of neural tube closure. VIP enhanced growth in whole cultured mouse embryos; treatment with a VIP antagonist during embryogenesis inhibited growth and development. VIP antagonist treatment during embryogenesis also had permane...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2007.04.004

    authors： Hill JM,Cuasay K,Abebe DT

    更新日期：2007-07-01 00:00:00

  • Permeability of the blood-brain barrier to HIV-1 Tat.

    abstract：:Infection with human immunodeficiency virus-1 (HIV-1) is associated with dysfunctions of the central nervous system (CNS). HIV-1 induces its effects on the CNS by a variety of mechanisms, including by shedding the neurotoxic viral proteins such as gp120 and Tat. Both HIV-1 and gp120 have been shown to cross the blood-...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2004.11.019

    authors： Banks WA,Robinson SM,Nath A

    更新日期：2005-05-01 00:00:00

  • Adenosine and propentofylline inhibit the proliferation of cultured microglial cells.

    abstract：:Propentofylline is a xanthine derivative that has been known to protec t neurons against ischemia-induced damage. To assess its neuroprotective mechanisms, we examined the effect of propentofylline on microglial proliferation that is thought to play an important role in neuronal damage. We determined the proliferation...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1006/exnr.1996.0035

    authors： Si QS,Nakamura Y,Schubert P,Rudolphi K,Kataoka K

    更新日期：1996-02-01 00:00:00

  • Ghrelin prevents 1-methyl-4-phenylpyridinium ion-induced cytotoxicity through antioxidation and NF-kappaB modulation in MES23.5 cells.

    abstract：:Ghrelin, a 28-amino acid peptide, is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. Our previous data showed that ghrelin could inhibit apoptosis in Parkinson's disease (PD) models both in vitro and in vivo. There is now growing evidence that oxidative stress has a critical role in the etiolo...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2009.11.009

    authors： Liu L,Xu H,Jiang H,Wang J,Song N,Xie J

    更新日期：2010-03-01 00:00:00

  • Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration.

    abstract：:Based on their differentiation ability, bone marrow stromal cells (MSCs) are a good source for cell therapy. Using a cynomolgus monkey peripheral nervous system injury model, we examined the safety and efficacy of Schwann cells induced from MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2010.01.022

    authors： Wakao S,Hayashi T,Kitada M,Kohama M,Matsue D,Teramoto N,Ose T,Itokazu Y,Koshino K,Watabe H,Iida H,Takamoto T,Tabata Y,Dezawa M

    更新日期：2010-06-01 00:00:00

  • Specific inhibition of myelination by lead in vitro; comparison with arsenic, thallium, and mercury.

    abstract：:Lead induces peripheral nerve segmental demyelination in rats. Arsenic and thallium produce a peripheral neuropathy characterized by axonal degeneration in humans. Mercury and thallium appear to damage both the peripheral and the central nervous system. It is not known whether this difference in effect is due to diffe...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(86)90283-9

    authors： Windebank AJ

    更新日期：1986-10-01 00:00:00

  • Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system.

    abstract：:Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low ...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2006.12.020

    authors： Hatcher JM,Richardson JR,Guillot TS,McCormack AL,Di Monte DA,Jones DP,Pennell KD,Miller GW

    更新日期：2007-04-01 00:00:00

  • Sexual dimorphism in the fibers of a "clasp" muscle of Xenopus laevis.

    abstract：:When antibodies specific to fast-twitch, slow-twitch, and slow-tonic myosins were used to stain the clasp muscle, m. sternoradialis, of Xenopus laevis, three predominant fiber types were identified in both males and females. Three fiber types can also be distinguished by the diameters and conduction velocities of thei...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/0014-4886(83)90414-4

    authors： Rubinstein NA,Erulkar SD,Schneider GT

    更新日期：1983-11-01 00:00:00

  • A reassessment of P2X7 receptor inhibition as a neuroprotective strategy in rat models of contusion injury.

    abstract：:These experiments were completed as part of an NIH "Facilities of Research Excellence in Spinal Cord Injury" contract to support independent replication of published studies that could be considered for eventual clinical testing. Recent studies have reported that selective inhibition of the P2X7 receptor improves both...

    journal_title：Experimental neurology

    pub_type： 杂志文章

    doi：10.1016/j.expneurol.2011.06.008

    authors： Marcillo A,Frydel B,Bramlett HM,Dietrich WD

    更新日期：2012-02-01 00:00:00

  • The role of growth factors as a therapeutic approach to demyelinating disease.

    abstract：:A variety of growth factors are being explored as therapeutic agents relevant to the axonal and oligodendroglial deficits that occur as a result of demyelinating lesions such as are evident in Multiple Sclerosis (MS). This review focuses on five such proteins that are present in the lesion site and impact oligodendroc...

    journal_title：Experimental neurology

    pub_type： 杂志文章,评审

    doi：10.1016/j.expneurol.2016.02.023

    authors： Huang Y,Dreyfus CF

    更新日期：2016-09-01 00:00:00