Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice

Yamashita, Naoya; Jitsuki-Takahashi, Aoi; Ogawara, Miyuki; Ohkubo, Wataru; Araki, Tomomi; Hotta, Chie; Tamura, Tomohide; Hashimoto, Shu-ichi; Yabuki, Takashi; Tsuji, Toru; Sasakura, Yukie; Okumura, Hitoshi; Takaiwa, Aki; Koyama, Chika; Murakami, Koji; Goshima, Yoshio

doi:10.1093/intimm/dxv014

Cited by 26 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antibodies are known for their large ''binding footprint'' and are promising in their inhibitory potential on ligand-receptor interactions. However, obtaining specific antibodies reactive with the functional interfaces on semaphorins and plexins, which are highly conserved across species, is generally very difficult and only a few examples have been reported (Fisher et al, 2016;Yamashita et al, 2015). In contrast, midsized drugs have gained much recent attention because of their ability to bear high affinity and specificity due to their similar binding surface area to antibodies, while being free from the dependence on the immune system (Gao et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Allosteric Inhibition of a Semaphorin 4D Receptor Plexin B1 by a High-Affinity Macrocyclic Peptide

Matsunaga

Bashiruddin

Kitago

et al. 2016

Cell Chemical Biology

View full text Add to dashboard Cite

Semaphorin axonal guidance factors are multifunctional proteins that play important roles in immune response, cancer cell proliferation, and organogenesis, making semaphorins and their signaling receptor plexins important drug targets for various diseases. However, the large and flat binding surface of the semaphorin-plexin interaction interface is difficult to target by traditional small-molecule drugs. Here, we report the discovery of a high-affinity plexin B1 (PlxnB1)-binding macrocyclic peptide, PB1m6 (K = 3.5 nM). PB1m6 specifically inhibited the binding of physiological ligand semaphorin 4D (Sema4D) in vitro and completely suppressed Sema4D-induced cell collapse. Structural studies revealed that PB1m6 binds at a groove between the fifth and sixth blades of the sema domain in PlxnB1 distant from the Sema4D-binding site, indicating the non-competitive and allosteric nature of the inhibitory activity. The discovery of this novel allosteric site can potentially be used to target plexin family proteins for the development of drugs that modulate semaphorin and plexin signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

Allosteric Inhibition of a Semaphorin 4D Receptor Plexin B1 by a High-Affinity Macrocyclic Peptide

Matsunaga

Bashiruddin

Kitago

et al. 2016

Cell Chemical Biology

View full text Add to dashboard Cite

show abstract

“…Next, we investigated the effect of an antibody to Sema3A on the regeneration of IAN by immunohistochemistry to confirm the involvement of Sema3A in IAN regeneration. The anti-Sema3A antibody used in this study has been reported to neutralize the effects of Sema3A in vitro 11 . Nerve fibers extending in random directions from the lesion were observed in the vehicle control animals treated with physiological saline (PS) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Following nerve transection, 10 μL (50 μg) of anti-Sema3A monoclonal antibody which was courtesy with Chiome Bioscience Inc., Tokyo, Japan was locally administered by a Hamilton Syringe to the transected area three times: immediately after surgery and at PO day 1 and PO day 2 under anesthesia by sevoflurane inhalation (n = 4). This anti-Sema3A antibody has proven effective in neutralizing the effects of Sema3A in vitro 11 . As a vehicle control (n = 3), 10 μL of PS was applied in the same manner.…”

Section: Methodsmentioning

confidence: 99%

Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection

Kanemaru

Yamada

Ohazama

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Neuroma formation at sites of injury can impair peripheral nerve regeneration. Although the involvement of semaphorin 3A has been suggested in neuroma formation, this detailed process after injury is not fully understood. This study was therefore undertaken to examine the effects of semaphorin 3A on peripheral nerve regeneration during the early stage after injury. Immunohistochemistry for semaphorin 3A and PGP9.5, a general neuronal marker, was carried out for clarify chronological changes in their expressions after transection of the mouse inferior alveolar nerve thorough postoperative days 1 to 7. At postoperative day 1, the proximal stump of the damaged IAN exhibited semaphorin 3A, while the distal stump lacked any immunoreactivity. From this day on, its expression lessened, ultimately disappearing completely in all regions of the transected inferior alveolar nerve. A local administration of an antibody to semaphorin 3A into the nerve transection site at postoperative day 3 inhibited axon sprouting at the injury site. This antibody injection increased the number of trigeminal ganglion neurons labeled with DiI (paired t-test, p < 0.05). Immunoreactivity of the semaphorin 3A receptor, neuropilin-1, was also detected at the proximal stump at postoperative day 1. These results suggest that nerve injury initiates semaphorin 3A production in ganglion neurons, which is then delivered through the nerve fibers to the proximal end, thereby contributes to the inhibition of axonal sprouting from the proximal region of injured nerves in the distal direction. To our knowledge, this is the first report to reveal the involvement of Sema3A in the nerve regeneration process at its early stage.

show abstract

“…A recent paper by Boggio et al () used adeno‐associated virus to overexpress the soluble fragment of neuropilin 1, the receptor of Sema3A, resulting in an enhanced ocular dominance plasticity in the visual cortex. Additionally, anti‐Sema3A monoclonal antibodies have been developed (Yamashita et al, ); while not being designed to specifically target Sema3A in the PNNs, these antibodies could be probed for their relevance in blocking Sema3A binding to PNNs both in vitro and in vivo.…”

Section: Modulation Of the Pnnsmentioning

confidence: 99%

The potential of memory enhancement through modulation of perineuronal nets

Duncan

Foster

Kwok

2019

British J Pharmacology

View full text Add to dashboard Cite

With an increasingly aging global population, the incidence of neurological diseases such as dementia is set to increase to unmanageable levels, yet there are currently only symptomatic therapies available for treatment. The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Specifically, condensed mesh‐like structures called perineuronal nets (PNNs) form around subsets of neurons and have a profound effect on axonal growth and limit neuronal plasticity. These PNNs act as a morphological checkpoint and can influence memory and cognition. Manipulating these important ECM structures may provide the key to reactivating plasticity and restoring memory, both of which are severely impaired in AD and other associated neurological diseases. This review explores the current understanding of how PNNs are manipulated and examines potential new methods for PNN modulation. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

show abstract

Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice

Cited by 26 publications

References 43 publications

Allosteric Inhibition of a Semaphorin 4D Receptor Plexin B1 by a High-Affinity Macrocyclic Peptide

Allosteric Inhibition of a Semaphorin 4D Receptor Plexin B1 by a High-Affinity Macrocyclic Peptide

Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection

The potential of memory enhancement through modulation of perineuronal nets

Contact Info

Product

Resources

About