Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

Namekata, Kazuhiko; Kimura, Atsuko; Kawamura, Kazuto; Guo, Xiaoli; Harada, Chikako; Tanaka, Kohichi; Harada, Takayuki

doi:10.1038/cdd.2013.91

Cited by 58 publications

(65 citation statements)

References 57 publications

(87 reference statements)

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Section: Discussionmentioning

confidence: 95%

“…11,31,44 In addition, overexpression of Dock3 suppressed retinal degeneration in GLAST KO mice. 11 Interestingly, Dock3 signaling is enhanced by brain-derived neurotrophic factor (BDNF), which induces neuroprotection, axonal outgrowth and neurogenesis. 31,[45][46][47] A recent study has shown that a novel phosphine-borane complex promotes RGC protection through the induction of BDNF and activation of the extracellular signal-regulated kinases (ERK) 1/2.…”

Section: Discussionmentioning

confidence: 95%

“…7 Together with the downregulation of glutamate transporters and glutathione levels observed in glaucoma patients, [8][9][10] these mice seem to be useful as the animal models of NTG. 6,[11][12][13][14][15] Polyamines have a plethora of effects on many aspects of neuronal behavior. They were previously reported to have an effect on neuritogenesis, 16 brain development, 17 neuronal survival, 18 and peripheral nerve regeneration.…”

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confidence: 99%

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Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma

Noro

Namekata

Azuchi

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To assess the therapeutic potential of spermidine in mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma.METHODS. Spermidine, at 30 mM in drinking water, was administered to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, and the measurement of intraocular pressure (IOP) were performed at 5, 8, and 12 weeks old. Histopathology analyses were carried out at 8 and 12 weeks old, and immunoblot and immunohistochemical analyses of 4-hydroxy-2-nonenal (4-HNE) in the retina were performed at 8 weeks old. RESULTS. Spermidine ameliorated retinal degeneration and improved visual function in EAAC1KO mice at both 8 and 12 weeks old, without affecting IOP. A significant increase of 4-HNE was observed in vehicle-treated EAAC1 KO mice, but spermidine treatment reduced this increase, suggesting that spermidine alleviated the severity of the glaucoma-like phenotype by acting as an antioxidant. CONCLUSIONS.The results from this study suggest that oral spermidine administration could be a useful treatment for retinal degenerative disorders including glaucoma.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

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Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma

Noro

Namekata

Azuchi

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…DOCK3 has been shown to be an essential regulator of cell movement and apoptosis via the modulation of RAC1 signaling by converting RAC1-GDP into RAC1-GTP via DOCK3's GTPase activity (66,76). Normal cellular migration and viability are significantly affected if DOCK3 is overexpressed or silenced, depending on the cell type (62,64).…”

Section: Dock3 Is An Essential Regulator Of Pten/akt and Rac1 Signalimentioning

confidence: 99%

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

Alexander¹,

Casar²,

Matsuki³

et al. 2014

J. Clin. Invest.

120

122

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Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which resultsin dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmd mdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmd mdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle-specific miR-486 overexpression in Dmd mdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle.

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“…[4][5][6] Also, inhibitors of glutamate receptors, tumor necrosis factor receptors, and nitric oxide synthase may be effective for RGC protection. [7][8][9][10][11] The ONI model mimics some aspects of glaucoma, including RGC death induced by oxidative stress, and therefore, it is also a useful animal model for glaucoma.…”

mentioning

confidence: 99%

Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury

Akiyama

Azuchi

Guo

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI).METHODS. Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI. Reactive oxygen species (ROS) levels were assessed with a CellROX Green Reagent.RESULTS. Edaravone ameliorated ONI-induced ROS production, RGC death, and inner retinal degeneration. Also, activation of the ASK1-p38 MAPK pathway that induces RGC death following ONI was suppressed with edaravone treatment. CONCLUSIONS.The results of this study suggest that intraocular administration of edaravone may be a useful treatment for posttraumatic complications.Keywords: edaravone, oxidative stress, neuroprotection, ASK1, retinal ganglion cell T raumatic optic neuropathy is a common clinical problem that occurs in 0.5% to 5% of patients with closed head injury.1 Damage to the optic nerve induces secondary swelling within the optic canal, accompanied by subsequent retinal ganglion cell (RGC) loss and optic nerve atrophy.2 Although no large natural history or randomized controlled trials have been published, corticosteroid therapy and optic canal decompression surgery are not considered to be effective for patients with traumatic optic neuropathy.3 Research into finding therapeutic targets for treatment of traumatic optic neuropathy indicated that neuroprotection might be an effective strategy and studies using an optic nerve injury (ONI) model in rodents have provided useful information. For example, neurotrophins, such as brain-derived neurotrophic factor and ciliary neurotrophic factor, protect retinal RGCs in an ONI model. [4][5][6] Also, inhibitors of glutamate receptors, tumor necrosis factor receptors, and nitric oxide synthase may be effective for RGC protection. 7-11The ONI model mimics some aspects of glaucoma, including RGC death induced by oxidative stress, and therefore, it is also a useful animal model for glaucoma.Edaravone is a free radical scavenger that has been used clinically to treat acute brain infarction and amyotrophic lateral sclerosis (ALS). Edaravone quenches hydroxyl radicals ( Á OH) and inhibits lipid peroxidation dependent and independent of Á OH. 12,13 In an in vitro cell culture study using the RGC-5 to study the neurobiology of RGCs, edaravone scavenged the intracellular Á OH, superoxide anion (O 2 ÀÁ ), and hydrogen peroxide (H 2 O 2 ) while demonstrating the strongest scavenging activity against14 Recent studies have shown that oxidative stress plays an important role in many ocular diseases including glaucoma. [15][16][17][18] Interestingly, edaravone attenuates retinal ischemia/reperfusion ...

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Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma

Cited by 58 publications

References 57 publications

Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma

Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury

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