scholarly journals Serine proteases, serine protease inhibitors, and protease-activated receptors: Roles in synaptic function and behavior

2011 ◽  
Vol 1407 ◽  
pp. 107-122 ◽  
Author(s):  
Antoine G. Almonte ◽  
J. David Sweatt
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Synaptic Function ◽  
Serine Protease Inhibitors ◽  
Protease Activated Receptors ◽  
And Behavior

scholarly journals Serine proteases and serine protease inhibitors in testicular physiology: the plasminogen activation system

Reproduction ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 721-729 ◽  
Author(s):  
Brigitte Le Magueresse-Battistoni
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Expression Pattern ◽  
Serine Proteases ◽  
Current Knowledge ◽  
Adult Life ◽  
Plasminogen Activation ◽  
Serine Protease Inhibitors ◽  
Plasminogen Activation System ◽  
Activation System

The testis is an organ in which a series of radical remodeling events occurs during development and in adult life. These events likely rely on a sophisticated network of proteases and complementary inhibitors, including the plasminogen activation system. This review summarizes our current knowledge on the testicular occurrence and expression pattern of members of the plasminogen activation system. The various predicted functions for these molecules in the establishment and maintenance of the testicular architecture and in the process of spermatogenesis are presented.

scholarly journals Therapeutic targeting of coronavirus spike glycoprotein priming

2020 ◽  
Author(s):  
Maurizio Pellecchia ◽  
Elisa Barile ◽  
Carlo Baggio ◽  
Luca Gambini ◽  
Sergey A. Shiryaev ◽  
...  
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Viral Proteins ◽  
Exact Nature ◽  
Cleavage Sites ◽  
Serine Protease Inhibitors ◽  
Spike Glycoprotein ◽  
Highly Pathogenic

Abstract Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2’) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species, and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2’ cleavage sites of their spike glycoprotein. However there remains some confusion on the relative roles of the possible serine-proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing virulence. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of the additional mutations in the S-protein priming sequence in coronaviruses.

Alpha-1 Antitrypsin Is a Potent Inhibitor of Cytokine-Induced Hematopoietic Stem Cell Mobilization.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1185-1185
Author(s):  
Melissa van Pel ◽  
Ronald van Os ◽  
Gerjo A. Velders ◽  
Henny Hagoort ◽  
Ivan J. Lindley ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Serine Protease ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Low Dose ◽  
Serine Protease Inhibitors ◽  
Hematopoietic Stem ◽  
Substrate Conversion

Abstract Previously, we have shown that IL-8 and G-CSF-induced hematopoietic stem cell (HSC) mobilization is inhibited in mice that underwent low dose (0.5 Gy) total body irradiation (TBI), whereas the number of progenitor cells in the bone marrow remained similar in all groups. The mechanism underlying this inhibition remains unknown. Since the release of granular proteases by neutrophils is well known to play a role in HSC mobilization, we also considered a possible role for serine protease inhibitors in the induction of HSC mobilization. Serine proteases, such as elastase and cathepsin G, are irreversibly inhibited by serine protease inhibitors including alpha-1 antitrypsin (alpha-1 AT) and alpha2-macroglobulin. In-vitro tests revealed that addition of bone marrow extracellular extracts, that were obtained from murine femurs 24 hours following low dose (0.5 Gy) TBI, inhibited the activity of exogenous elastase in a chromogenic substrate conversion assay up to 78.1 % compared to extracts obtained from sham irradiated controls (p<0.05). Since elastase inhibition by alpha2-macroglobulin cannot be detected in a chromogenic substrate conversion assay, alpha-1 AT was considered as the primary candidate serine protease inhibitor to inhibit elastase activity in our in-vitro system. Quantitative PCR of total bone marrow cells revealed that alpha-1 AT mRNA was 20-fold increased relative to the housekeeping gene ß-actin and 7-fold relative to the housekeeping genes HPRT and GAPDH at 24 hours following low dose (0.5 Gy) TBI. In addition, Western blot analysis indicated that alpha-1 AT protein concentrations were significantly (p<0.01) increased in bone marrow extracellular extracts derived from low dose (0.5 Gy) irradiated mice, compared to extracts obtained from sham-irradiated controls (5.1 ± 0.6 scanning units [SU] vs. 3.9 ± 0.7 SU for 0.5 Gy;n=8 vs. 0 Gy; n=6 respectively). To further substantiate a possible in-vivo role of alpha-1 AT in the inhibition of HSC mobilization, we administered alpha-1 AT (300 μg/mouse i.p.) at 2 hours and at 5 minutes prior to IL-8 injection (30 μg/mouse i.p.). Administration of alpha-1 AT prior to IL-8 injection completely (p<0.05) inhibited IL-8-induced HSC mobilization (472.9 ± 289.5 CFU-GM per ml blood for IL-8; n=5 vs. 44.8 ± 35.5 CFU-GM per ml blood for alpha-1 AT/IL-8; n =11). These results indicate that 1) alpha-1 AT is a potent inhibitor of IL-8-induced HSC mobilization and 2) in-vivo induced alpha-1 AT contributes to the inhibition of HSC mobilization after low-dose (0.5 Gy) TBI. We hypothesize that a critical balance between serine proteases and serine protease inhibitors plays an important role in cytokine-induced HSC mobilization.

Regulation of kallikrein-related peptidases in the skin – from physiology to diseases to therapeutic options

2013 ◽  
Vol 110 (09) ◽  
pp. 442-449 ◽  
Author(s):  
Jan Fischer ◽  
Ulf Meyer-Hoffert
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Therapeutic Intervention ◽  
Serine Proteases ◽  
Current Knowledge ◽  
Serine Protease Inhibitors ◽  
Specific Expression ◽  
Physiological Processes ◽  
Promising Target ◽  
Protease Activation

SummaryKallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases, which show a tissue-specific expression profile. This made them valuable tumour expression markers. It became evident that KLKs are involved in many physiological processes like semen liquefaction and skin desquamation. More recently, we have learnt that they are involved in many pathophysiological conditions and diseases making them promising target of therapeutic intervention. Therefore, regulation of KLKs raised the interest of numerous reports. Herein, we summarise the current knowledge on KLKs regulation with an emphasis on skin-relevant KLKs regulation processes. Regulation of KLKs takes place on the level of transcription, on protease activation and on protease inactivation. A variety of protease inhibitors has been described to interact with KLKs including the irreversible serine protease inhibitors (SERPINs) and the reversible serine protease inhibitors of Kazal-type (SPINKs). In an attempt to integrate current knowledge, we propose that KLK regulation has credentials as targets for therapeutic intervention.

scholarly journals Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2424 ◽  
Author(s):  
Elisa Barile ◽  
Carlo Baggio ◽  
Luca Gambini ◽  
Sergey A. Shiryaev ◽  
Alex Y. Strongin ◽  
...  
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Serine Proteases ◽  
Viral Proteins ◽  
Exact Nature ◽  
Cleavage Sites ◽  
Serine Protease Inhibitors ◽  
Spike Glycoprotein ◽  
Highly Pathogenic

Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2′ cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.

scholarly journals Hindrance of the Proteolytic Activity of Neutrophil-Derived Serine Proteases by Serine Protease Inhibitors as a Management of Cardiovascular Diseases and Chronic Inflammation

2021 ◽  
Vol 9 ◽  
Author(s):  
Timo Burster ◽  
Zhadyra Mustafa ◽  
Dinara Myrzakhmetova ◽  
Anuar Zhanapiya ◽  
Michal Zimecki
Keyword(s):  
Cardiovascular Diseases ◽  
Serine Protease ◽  
Chronic Inflammation ◽  
Protease Inhibitors ◽  
Proteolytic Activity ◽  
Serine Proteases ◽  
Logical Consequence ◽  
Immune Defense ◽  
Serine Protease Inhibitors ◽  
Surrounding Environment

During inflammation neutrophils become activated and segregate neutrophil serine proteases (NSPs) to the surrounding environment in order to support a natural immune defense. However, an excess of proteolytic activity of NSPs can cause many complications, such as cardiovascular diseases and chronic inflammatory disorders, which will be elucidated on a biochemical and immunological level. The application of selective serine protease inhibitors is the logical consequence in the management of the indicated comorbidities and will be summarized in this briefing.

scholarly journals Serine Protease Inhibitors: Novel Therapeutic Targets for Stroke?

2000 ◽  
Vol 20 (5) ◽  
pp. 755-764 ◽  
Author(s):  
Denis Vivien ◽  
Alain Buisson
Keyword(s):  
Extracellular Matrix ◽  
Middle Cerebral Artery ◽  
Serine Protease ◽  
Plasminogen Activator ◽  
Protease Inhibitors ◽  
Cerebral Artery ◽  
Neuronal Death ◽  
Serine Proteases ◽  
Infarct Volume ◽  
Serine Protease Inhibitors

Although the thrombolytic activity of tissue-type plasminogen activator (t-PA) may be beneficial in the acute treatment of stroke, recent studies have suggested that this serine protease could also play a critical role in determining the extent of neuronal death after injury to the central nervous system (CNS). This hypothesis is based on several experimental results: t-PA-deficient mice are resistant to excitotoxic neuronal death induced by the intrahippocampal injection of kainate; the infarct volume induced by occlusion of the middle cerebral artery is reduced in t-PA knockout mice; and the intravenous injection of t-PA can under certain circumstances potentiate the infarct volume in animals subjected to middle cerebral artery occlusion. In the CNS, the serine proteases have been identified to occur both in neurons and glial cells. Their enzymatic activity regulates the balance between the accumulation and the degradation of the extracellular matrix. They are involved in many physiologic functions, ranging from synaptic outgrowth during perinatal development to plasticity in adults. For instance, thrombin and t-PA are known to modulate neurite outgrowth and tissue remodeling in the early stages of development. In the adult brain, t-PA may contribute to the late phase of long-term potentiation and to the subsequent synaptic growth in the hippocampal mossy fiber pathway. This balance between the degradation and accumulation of the extracellular matrix may also be integral to various pathologic processes involved in acute brain injury. For example, compounds that modulate the activity of serine proteases exhibit neuroprotective activity. Based on the above, numerous studies have focused on the production and modulation of the endogenously produced serine protease inhibitors, termed serpins, such as type 1 plasminogen activator inhibitor, neuroserpin, and protease nexin-1. In the present review, we will discuss the need to distinguish between the potentially neurotoxic effects of t-PA and its beneficial effect on reperfusion. We will present data supporting the idea that the modulation of serine protease activity may represent a novel and efficient strategy for the treatment of acute cerebral injury in humans.

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