- |||||||||| Lexiscan (regadenoson) / Astellas, GE Healthcare, Gilead
Journal: Hydroxysafflor Yellow A Together with Blood-Brain Barrier Regulator Lexiscan for Cerebral Ischemia Reperfusion Injury Treatment. (Pubmed Central) - Aug 11, 2020
Lastly, HSYA together with Lex (Lex-HSYA) could significantly reduce the volume of cerebral infarction, improve the histopathological morphology, and recruit brain-derived neurotrophic factors to alleviate the cerebral ischemia reperfusion injury. In conclusion, the pyroptosis pathway could act as a novel therapeutic target of HSYA in nerve injury treatment, and Lex-HSYA could be a promising candidate for nerve injury treatments.
- |||||||||| Review, Journal: Immunological approaches and therapy in burns (Review). (Pubmed Central) - Aug 9, 2020
Severe burns require nutritional support and pharmacotherapy not only for burn area but for different pathological complications of burn injury. In-depth research is required to find new ways to modulate the defense capacity, to prevent the complications of abnormal immune response and to treat burn injuries efficiently.
- |||||||||| Review, Journal: Aseptic Μeningitis in Hereditary Autoinflammatory Diseases. (Pubmed Central) - Aug 9, 2020
Herein, the aim of this review article is to describe the association between aseptic meningitis and ADs, especially in patients with familial Mediterranean fever (FMF) and chronic infantile neurological cutaneous articular (CINCA) syndrome. We will discuss the emerging role of proinflammatory cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in the pathogenesis of aseptic meningitis in ADs, and will explore recent treatment developments, such as the use of biological agents.
- |||||||||| Journal: Blocking inflammasome activation caused by β-amyloid peptide (Aβ) and islet amyloid polypeptide (IAPP) through an IAPP mimic. (Pubmed Central) - Aug 8, 2020
Moreover, in contrast to IAPP aggregates, IAPP/IAPP-GI hetero-oligomers become rapidly internalized and degraded in the lysosomal compartments of macrophages. Our findings uncover a previously unknown function for the IAPP/Aβ cross-amyloid interaction and suggest that conversion of Aβ or IAPP into lysosome-targeted and easily degradable hetero-oligomers by hetero-association with IAPP mimics could become a promising approach to specifically prevent amyloid-mediated inflammation in AD, T2D or both diseases.
- |||||||||| Review, Journal: Innate Immune Receptors, Key Actors in Cardiovascular Diseases. (Pubmed Central) - Aug 8, 2020
The classic PRRs, toll-like receptors (TLRs), and the more recently discovered nucleotide-binding oligomerization domain-like receptors (NLRs), have been recently proposed as key partners in the progression of several CVDs (e.g., atherosclerosis and heart failure). The present review discusses the key findings related to the involvement of TLRs and NLRs in the progression of several vascular and cardiac diseases, with a focus on whether some NLR subtypes (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor 3 and nucleotide-binding oligomerization domain-containing protein 1) can be candidates for the development of new therapeutic strategies for several CVDs.
- |||||||||| sirolimus / Generic mfg.
Journal: Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. (Pubmed Central) - Aug 6, 2020
Thus, we demonstrated that Ka promotes neuroinflammatory inhibition via the cooperation of ubiquitination and autophagy, suggesting that Ka is a promising therapeutic strategy for the treatment of NDDs. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A BECN1: beclin 1, autophagy related; CASP1: caspase 1; CNS: central nervous system; CQ: chloroquine; DA neurons: dopaminergic neurons; DAMPS: damage-associated molecular patterns; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFAP: glial fibrillary acidic protein; IP: immunoprecipitation; i.p.: intraperitoneally; Ka: kaempferol; KD: knockdown; KO: knockout; LPS: lipopolysaccharide; IL1B: interleukin 1 beta; IL6: interleukin 6; Ly: lysate; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NC: negative control; NDD: neurodegenerative diseases; NLRP3: NLR family, pyrin domain containing 3; OE: overexpression; PD: Parkinson disease; poly-Ub: poly-ubiquitin; PTM: post-translational modification; PYCARD/ASC: PYD and CARD domain containing; Rapa: rapamycin; RFP: red fluorescent protein; SN: supernatant; SNCA: synuclein alpha; SNpc: substantia nigra pars compacta; SQSTM1: sequestosome 1; TH: tyrosine hydroxylase; TNF/TNF-alpha: tumor necrosis factor; Ub: ubiquitin; WT: wild type.
- |||||||||| Rizaben (tranilast) / Kissei, Nuon Therapeutics
Journal: Tranilast Directly Targets NLRP3 to Protect Melanocytes From Keratinocyte-Derived IL-1β Under Oxidative Stress. (Pubmed Central) - Aug 6, 2020
Additionally, TR could mitigate the secretion of inflammatory cytokines such as IL-6, IL-8, TNF-α, and IL-18 in keratinocytes under oxidative stress. In short, our data indicate that IL-1β plays detrimental roles in the melanocyte survival, melanogenesis, melanosome translocation and the secretion of inflammatory cytokines, and TR could be a promising therapeutic strategy in vitiligo by attenuating the keratinocyte-derived IL-1β under oxidative stress.
- |||||||||| Preclinical, Journal, Epigenetic controller: In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study. (Pubmed Central) - Aug 6, 2020
It was observed that silencing of KDM5A didn't alter the levels of neither of the NLRP3 component but inhibition of LSD2 showed significant effect on NLRP3 expression while no change in caspase-1 and IL-1β levels. This study suggests that rather LSD2 not KDM5A lysine demethylase family might be involved in the regulation of NLRP3 inflammasome in cancer cells which could be useful for deciphering the future therapeutic targets for the disease.
- |||||||||| Journal: Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome. (Pubmed Central) - Aug 4, 2020
Our studies suggest, for the first time, that propofol-induced pyroptosis might be restricted to macrophage through an NLRP3/ASC/caspase-1 pathway, which provides potential targets for limiting adverse reactions during propofol application. These findings demonstrate that propofol overdose can trigger cell death through caspase-1 activation and offer new insights into the use of anaesthetic drugs.
- |||||||||| Journal: The role of microglia mediated pyroptosis in neonatal hypoxic-ischemic brain damage. (Pubmed Central) - Aug 4, 2020
Mechanistically, we showed that NLRP-3/caspase-1/GSDMD axis is required for microglia pyroptosis and activation. Our data demonstrated that microglia mediated pyroptosis played a crucial role in neonatal HIE, which shed lights into the development of intervention avenues targeting pyroptosis to treat HIE and traumatic brain injuries.
- |||||||||| Review, Journal: Targeting the NLRP3 Inflammasome in Severe COVID-19. (Pubmed Central) - Aug 4, 2020
This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.
- |||||||||| Kineret (anakinra) / SOBI, Affibody
[VIRTUAL] Outcome of cochlear implantation in NLRP3 -related autoinflammatory inner ear disorders (E-Poster Area) - Aug 4, 2020 - Abstract #ESHG2020ESHG_2325;
This is the first report to present outcome of CI among subjects with a confirmed NLRP3 genetic etiology and resultant systemic inflammation, and suggests that CI is a viable treatment option in this disease entity. Grant references: Ministry of Education (2018R1A2B2001054BYC) Ministry of Health & Welfare (HI17C0952BYC) SNUBH Research Fund (13-2020-013BYC) CNUH Research Fund, 2019 (BJK)
- |||||||||| Review, Journal: Role of the NLRP3 inflammasome in autoimmune diseases. (Pubmed Central) - Aug 3, 2020
In this review, we briefly introduce the biological features of the NLRP3 inflammasome and present the mechanisms underlying its activation and regulation. We also summarize recent studies that have reported on the roles of NLRP3 inflammasome in the immune system and several autoimmune diseases, with a focus on therapeutic and clinical applications.
- |||||||||| [VIRTUAL] Innate immune activation of the NLRP3 inflammasome pathway drives tau pathology (Virtual Room Name: Rotterdam) - Aug 2, 2020 - Abstract #AAIC2020AAIC_4465;
These findings are in line with the hypothesis that innate immune activation represents an important pathogenic factor for tau pathology. In Alzheimers disease, early A deposition may cause subsequent tau pathology and neuronal demise through NLRP3-mediated innate immune pathways.
- |||||||||| [VIRTUAL] 25-hydroxycholesterol amplifies microglial IL-1beta production in an apoE isoform dependent manner (Virtual Room Name: Session Chatroom) - Aug 2, 2020 - Abstract #AAIC2020AAIC_4232;
In Alzheimers disease, early A deposition may cause subsequent tau pathology and neuronal demise through NLRP3-mediated innate immune pathways. 25-HC may function as a microglial secreted inflammatory mediator in brain, promoting IL-1b-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.
- |||||||||| [VIRTUAL] 25-hydroxycholesterol amplifies microglial IL-1beta production in an apoE isoform dependent manner () - Aug 2, 2020 - Abstract #AAIC2020AAIC_4228;
25-HC may function as a microglial secreted inflammatory mediator in brain, promoting IL-1b-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD. 25-HC may function as a microglial secreted inflammatory mediator in brain, promoting IL-1b-mediated neuroinflammation in an apoE isoform-dependent manner (E4>>E2/E3) and thus may be an important mediator of neuroinflammation in AD.
- |||||||||| [VIRTUAL] Investigating markers of NLRP3 inflammasome activation in neurodegenerative diseases () - Aug 2, 2020 - Abstract #AAIC2020AAIC_2104;
Although our data are contrary to previous findings from in vitro and in vivo preclinical studies, they are similar to other two post-mortem human brain studies. It may be that data from animal models and in vitro studies, in which inflammatory processes are usually generated acutely with abundant stimuli, are not representative of the chronic neuroinflammation associated with neurodegenerative diseases.
- |||||||||| dexamethasone / Generic mfg.
[VIRTUAL] Inflammasome activation and reduced sTREM2 release in LPS stimulated organotypic brain slices () - Aug 2, 2020 - Abstract #AAIC2020AAIC_1684;
Disease-relevant pathways are activated by LPS stimulation and this process can be reversed by some reference compounds. By maintaining the three-dimensional structure and interplay of different cell types of the postnatal brain, this system closely resembles the in vivo situation while offering several advantages for early screenings, like sampling of supernatant at various time points and higher trough-put.
- |||||||||| [VIRTUAL] NLRP3 inflammasome activation regulates microglial migration (Virtual Room Name: Session Chatroom) - Aug 2, 2020 - Abstract #AAIC2020AAIC_1040;
Critically, this activity is increased in NLRP3-/- cells or those treated with NLRP3-specific inhibitors, together demonstrating a previously unknown role for the NLRP3 inflammasome in regulating cellular migratory and phagocytic behavior. These findings provide insights into the pathogenesis of AD and importantly highlight the NLRP3 inflammasome as a serious target for prevention and early treatment of AD.
- |||||||||| [VIRTUAL] NLRP3 inflammasome activation regulates microglial migration () - Aug 2, 2020 - Abstract #AAIC2020AAIC_1036;
Critically, this activity is increased in NLRP3-/- cells or those treated with NLRP3-specific inhibitors, together demonstrating a previously unknown role for the NLRP3 inflammasome in regulating cellular migratory and phagocytic behavior. These findings provide insights into the pathogenesis of AD and importantly highlight the NLRP3 inflammasome as a serious target for prevention and early treatment of AD.
- |||||||||| [VIRTUAL] The Impact of the Intestinal Microbiome On Microglial Inflammation () - Aug 2, 2020 - Abstract #AAIC2020AAIC_318;
The proposed research is significant because it suggests that bacteria found in the mammalian intestine can influence microglia in the brain and therefore may critically influence neurodegenerative disease such as AD. Identification of the intestinal microbiota as a factor that promotes microglial inflammation and dysfunction will lay the groundwork for the development of therapeutic approaches that target the microbiota (i.e., consumption of prebiotics or probiotics) to prevent and treat age-associated diseases, such as AD.
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