Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: Implications for a therapeutic design

Gutiérrez-Franco, Ana; Costa, Carme; Eixarch, Herena; Castillo, Mireia; Medina‐Rodriguez, Eva M.; Bribián, Ana; Castro, Fernando de; Montalbán, Xavier; Espejo, Carmen

doi:10.1016/j.clim.2015.12.005

Cited by 28 publications

(21 citation statements)

References 66 publications

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“…These pathways contain differentially expressed genes encoding multiple proteins that are known to be associated axon and synapse dysfunction or degeneration in other neurodegenerations. These include multiple members of the ephrin family of receptors ( Epha2, Epha4, Epha5, Epha6, Ephb2, Ephb3, Ephb4 Ephb6 ; Chen et al, 2012), metabotropic glutamate receptors ( Grm3, Grm5, Grm6, Grm7 ; Ribeiro et al, 2017), Ryr3 (Balschun et al, 1999; Del Prete et al, 2014), and semaphorins ( Sema3a, Sema3b, Sema3d, Sema4a, Sema5a, Sema6a, Sema6c, Sema7a ; Shirvan et al, 2002; Good et al, 2004; Pasterkamp and Giger, 2009; Smith et al, 2015; Gutiérrez-Franco et al, 2016). There are no significantly enriched pathways in D2 Group 1 or D2 + NAM samples compared to controls.…”

Section: Resultsmentioning

confidence: 99%

Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

et al. 2017

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Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD+ and NADH) rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses. The Wallerian degeneration slow allele, WldS, decreases the vulnerability of retinal ganglion cells in eyes with elevated IOP, but the exact mechanism(s) of protection from glaucoma are not determined. Here, we demonstrate that WldS increases retinal NAD levels. Coupled with nicotinamide administration (an NAD precursor), it robustly protects from glaucomatous neurodegeneration in a mouse model of glaucoma (94% of eyes having no glaucoma, more than WldS or nicotinamide alone). Importantly, nicotinamide and WldS protect somal, synaptic, and axonal compartments, prevent loss of anterograde axoplasmic transport, and protect from visual dysfunction as assessed by pattern electroretinogram. Boosting NAD production generally benefits major compartments of retinal ganglion cells, and may be of value in other complex, age-related, axonopathies where multiple neuronal compartments are ultimately affected.

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Section: Resultsmentioning

confidence: 99%

Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

et al. 2017

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“…Sema7A expression in CNS on oligodendrocyte progenitor cells as well as in mature oligodendrocytes and immune cells is upregulated during EAE progression (Gutiérrez-Franco et al, 2016 ). This, together with other discussed above studies (Suzuki et al, 2007 ; Czopik et al, 2006 ), supports Sema7A involvement in disease pathogenesis and its potential as a therapeutic target in MS.…”

Section: Introductionmentioning

confidence: 99%

Neuroimmune semaphorins as costimulatory molecules and beyond

Chapoval

2018

Mol Med

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Several neuronal guidance proteins, known as semaphorin molecules, function in the immune system. This dual tissue performance has led to them being defined as “neuroimmune semaphorins”. They have been shown to regulate T cell activation by serving as costimulatory molecules. Similar to classical costimulatory molecules, neuroimmune semaphorins are either constitutively or inducibly expressed on immune cells. In contrast to the classical costimulatory molecule function, the action of neuroimmune semaphorins requires the presence of two signals, the first one provided by TCR/MHC engagement, and the second one provided by B7/CD28 interaction. Thus, neuroimmune semaphorins serve as a “signal three” for immune cell activation and regulate the overall intensity of immune response. The current knowledge on their structures, multiple receptors, specific cell/tissue/organ expression, and distinct functions in different diseases are summarized and discussed in this review.

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“…On the basis of a previous study ( 25 ) demonstrating that SEMA7A regulates neutrophil trafficking during acute pulmonary inflammation, the present study assessed SEMA-7A expression in rats with lung injury induced by LPS (500 µg/kg) in vivo . Levels of SEMA-7A mRNA and protein expression were significantly higher in the pulmonary tissue of rats with lung injury (P<0.05; Fig.…”

Section: Resultsmentioning

confidence: 99%

Anti-Semaphorin-7A single chain antibody demonstrates beneficial effects on pulmonary inflammation during acute lung injury

et al. 2018

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Pulmonary inflammation is a primary characteristic of lung injury initiated by the accession of immune cells into the alveolar space. Neutrophil migration serves an important role in pulmonary inflammation mediated by the migration of neutrophils into hypoxic tissue sites. The elimination of pulmonary inflammation is directly associated with rehabilitation in patients with lung injury. Anti-inflammatory treatment is essential following lung injury and ultimately determines patient outcomes. Semaphorin-7A (SEMA-7A) is a member of the Semaphorin family that influences the migration of neutrophils into hypoxic tissue sites, thus promoting inflammation. However, understanding of the role of SEMA-7A serves during lung injury is limited and the immunological function of SEMA-7A during the migration of neutrophils into acute injury sites remains unknown. The present study investigated SEMA-7A expression and constructed a single chain antibody for SEMA-7A (Anti-SEMA-7A) to study its therapeutic efficacy against pulmonary inflammation in a mouse model of acute injury sites. The data indicated that the expression of SEMA-7A was upregulated due to induction by pro-inflammatory cytokines and demonstrated that Anti-SEMA-7A inhibited SEMA-7A expression in vitro and in vivo. The current study also indicated that the production of pro-inflammatory cytokines induced by SEMA-7A in endothelial and epithelial cells enhanced pulmonary inflammation. Anti-SEMA-7A suppressed the transendothelial migration of neutrophils mediated by SEMA-7A. Anti-SEMA-7A treatment neutralized SEMA-7A expression and reduced signs of pulmonary inflammation, leading to the elimination of pulmonary inflammation in rat with acute lung injury. The current study identified Anti-SEMA-7A as a potential agent to interfere with the inflammatory pathway during acute lung injury, which may be the basis for anti-inflammatory strategies to treat lung injuries in the future.

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Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: Implications for a therapeutic design

Cited by 28 publications

References 66 publications

Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

Neuroimmune semaphorins as costimulatory molecules and beyond

Anti-Semaphorin-7A single chain antibody demonstrates beneficial effects on pulmonary inflammation during acute lung injury

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