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Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
Neurons lengthen their axons in excess of extensive distances during developing connections with other synaptic neurons. Proteins involved in guiding the axon may control the progression of axon guidance. These proteins can play a function in attracting or repelling axons thus guide them to a definite area or stopping them from rising into unsuitable regions, correspondingly. Recently several report sustain the testing theory that abnormal expression or function of axon guiding proteins such as ephrins, semaphorins, slits, and netrins usually implicated in curating and maintaining circuits of motor neuron may bring on pathological variations in circuits of motor neuron (Hollis, 2015). Interestingly, pathological variations occurring in nerve terminals and motor axons are found to lead degeneration of motor neurons and associated clinical abnormalities (Fischer et al., 2004). It can be inferred from this discovery that the disease development may begin at the nerve endings and ultimately grow toward the body of the neuronal cell. Numerous diverse molecules responsible for guiding the axons changed expressions in patients of ALS. Thus single-nucleotide polymorphisms (SNPs) in genes expressing proteins for axon guidance may important for diagnosis of ALS (Lesnick et al., 2008). After realizing the importance of these proteins, recently the cell replacement strategies have been designed for corrections of the degenerating motor system of these patients (Silva and Yu, 2008).
Genetics in Otology and Neurotology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
The contribution of abnormal angiogenesis has recently been recognized in benign tumours and provides a novel therapeutic target for NF2-associated vestibular schwannomas. Vestibular schwannomas and peripheral schwannomas have been shown to express vascular endothelial growth factor (VEGF) in both tumour cells and associated endothelial cells.60, 61 Recent studies indicated that Merlin also regulates angiogenesis via semaphorin 3F (SEMA3F), a protein that inhibits angiogenesis.62 On these observations, bevacizumab, an angiogenesis inhibitor, is being used in at least two clinical trials.
Osteoimmunology in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Lia Ginaldi, Daniela Di Silvestre, Maria Maddalena Sirufo, Massimo De Martinis
Many other receptor pathways, most of which are shared by immune cells, interact with RANK, some co-stimulators and others inhibitors. The inhibitor receptor system ephrin (Eph) B2/B4 allows the passage of signals bidirectionally between osteoclasts and osteoblasts [54]. It inhibits osteoclast differentiation by blocking c-fos and the NFATc1 transcriptional cascade in osteoclast cell lineage and contemporaneously favors the coupling of bone formation and resorption through the induction of osteogenetic regulatory genes in osteoblasts [55]. The ephrinB2/ephrinB4 binding therefore functions as a coupling factor in bone remodeling process [56]. Other coupling factors are semaphorins, glycoproteins involved in several biological processes such as immune response, tumor progression, and bone remodeling, among others [57–59]. Semaphorin4D (Sema4D) expressed in osteoclasts binds to its osteoblast receptor (Plexin-B1) inhibiting IGF-1 pathway, essential for osteoblast differentiation [60], whereas Sema3A in osteoblasts is an inhibitor of osteoclastogenesis [61]. During bone remodeling osteoclasts inhibit bone formation by expressing Sema4D, in order to initiate bone resorption, whereas osteoblasts express Sema3A that suppresses bone resorption, prior to bone formation.
Semaphorin 3A Inhibits Endoplasmic Reticulum Stress Induced by High Glucose in Müller Cells
Published in Current Eye Research, 2023
Mengyang Li, Enzhong Jin, Li Zhu, Chi Ren, Zhiqiao Liang, Mingwei Zhao, Jinfeng Qu
Semaphorins, originally discovered by Kolodkin et al. in 1992,7 constitute a large family of endogenous secreted and transmembrane-associated proteins.8 Semaphorins have been characterized as repulsive axonal and vessel network guidance signals that regulate cellular interactions as well as cell differentiation, morphology, and function.9 The secreted protein Sema3A (collapsin-1) was the first vertebrate Semaphorin identified, and its role is to induce contraction and collapse of structures on axon growth cones.10 During signaling, Sema3A binds to the Plexin A 1-4 receptor, and Neuropilins 1 (Nrp-1) acts as a coreceptor to stabilize the Semaphorin-Plexin interaction.9 Since the discovery of Sema3A, the most studied function of Sema3A has been the effect on axon growth and neural repair during development and wound healing.11 A variety of studies have reported the effects of Sema3A on other physiological processes, including the immune response, organogenesis, tumor formation, and bone tissue remodeling.12 However, the effects of Sema3A on Müller cells in DR have not been documented.
Components of specific immunity in host defense
Published in International Reviews of Immunology, 2021
The dynamicity of immune cells and soluble mediatiors are key for host defense and immune homeostasis. It is mediated through Immune cell trafficking via complex signaling pathways. The movement of immune cells are primarily supported by cell surface molecule like leukocyte adhesion molecules, integrins, lectins, tetraspanines, and/or induction of chemokines and chemokine receptors and so on. A member of the semaphorin family protein known as semaphorin 4 D (Sema4D) is reported to play an important role in axon guidance and an important role in immunity, particularly, cell migration. The second review in this issue by Kuklin et al. discusses the role of Sema4D in immune regulation in cell migration. The article also discusses the underline molecular mechanism of Sema4D-mediated cell migration [2]. This article will be interesting to immunologists, neurologists, and scientists working in neuroimmunology (Figure 1).
New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials
Published in Expert Opinion on Investigational Drugs, 2020
Danilo Rocco, Vanesa Gregorc, Luigi Della Gravara, Chiara Lazzari, Giovanni Palazzolo, Cesare Gridelli
Semaphorins are a superfamily of secreted proteins involved in immune cell regulation, angiogenesis, and cancer progression. Semaphorin 4D (SEMA4D) also known as CD100, originally described in immune cells [125], was the first identified with immune-regulatory activity. Two isoforms are known, including a transmembrane full-length isoform, and a soluble molecule, originating from proteolytic cleavage of the cellular form [126]. SEMA4D is expressed on resting T cells, NK cells, tumor-associated macrophages, and neutrophils [127]. Data in vitro indicate that SEMA4D promotes tumor progression [128] and favors the release of immunosuppressive cytokines. Conversely, its inhibition determines the increase of effector T cells and the decrease of suppressive T regulatory cells. SEMA4D prevents the infiltration of immune cells within the TME, and its blockade is associated with immune infiltration and immune response in murine models of colon cancer and ERBB2+ breast carcinoma [129] resulting in an increased number of CD86+ APCs, CD8+ cytotoxic T cells and T effector/T regulatory cell ratio, with a decrease in MDSCs. However, evidences indicate that SEMA4D has a dual role: its downregulation in CD8+ and CD4 + T-cells is associated with impaired T-cells function, and its expression on dendritic cells induces their maturation, which further contributes to enhance activation of T-cells [130,131]. Moreover, in preclinical models of NSCLC, overexpression of SEMA4D has been described, alongside with the above-mentioned immunomodulatory effects [132].