Abstract:
:NLRP3-PYD inflammasome activates an inflammatory pathway in response to a wide variety of cell damage or infections. Dysregulated NLRP3 inflammatory signaling has many chronic inflammatory and autoimmune disorders. NLRP3 and ASC have a PYD, a superfamily member of the Death Domain, which plays a key role in inflammatory assembly. The ASC interacts with NLRP3 through a homotypic PYD and recruits the procaspase-1 through a homotypic caspase recruitment domain interaction. Here, we used several computational approaches to reveal the interactions of the NLRP3 and ASC PYD domains that lead to the activation of the inflammasome complex. We have characterized ASC and NLRP3-PYD intermolecular interactions by protein-protein docking, and further molecular dynamics (MD) simulations were conducted to evaluate the stability of NLRP3/ASC-PYD complex. Subsequently, we have identified several residues that stabilize the NLRP3/ASC-PYD complex in different faces (i.e., Face-1 to Face-4). The research framework offers new insights into the molecular mechanisms of inflammasome and apoptosis signaling as well as the ease of the drug discovery process.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Riaz M,Rehman AU,Shah SA,Rafiq H,Lu S,Qiu Y,Wadood Adoi
10.1021/acschemneuro.0c00519subject
Has Abstractpub_date
2021-01-27 00:00:00issn
1948-7193pub_type
杂志文章abstract::Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00390
更新日期:2019-02-20 00:00:00
abstract::Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, wh...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00060
更新日期:2015-06-17 00:00:00
abstract::Development of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00205
更新日期:2019-06-19 00:00:00
abstract::The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 μg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal inject...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn900005d
更新日期:2010-02-17 00:00:00
abstract::Alzheimer's disease is characterized by pathological aggregation of protein tau and amyloid-β peptides, both of which are considered to be toxic to neurons. Naturally occurring dietary flavonoids have received considerable attention as alternative candidates for Alzheimer's therapy taking into account their antiamyloi...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn400213r
更新日期:2014-02-19 00:00:00
abstract::Many physiological pathways are involved in appetite, food intake, and the maintenance of energy homeostasis. In particular, neuropeptides within the central nervous system have been demonstrated to be critical signaling molecules for modulating appetite. Both anorexigenic (appetite-decreasing) and orexigenic (appetit...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00151
更新日期:2018-06-20 00:00:00
abstract::Tropomyosin receptor kinases (TrkA/B/C) are critically involved in the development of the nervous system, in neurological disorders as well as in multiple neoplasms of both neural and non-neural origins. The development of Trk radiopharmaceuticals would offer unique opportunities toward a more complete understanding o...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500193f
更新日期:2015-02-18 00:00:00
abstract::The finding that acetylcholinesterase (AChE) colocalizes with β-amyloid (Aβ) and promotes and accelerates Aβ aggregation has renewed an intense interest in developing new multifunctional AChE inhibitors as potential disease-modifying drugs for Alzheimer's therapy. To this end, we have developed a new class of selectiv...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn100069c
更新日期:2010-11-17 00:00:00
abstract::Savella (milnacipran), a selective serotonin and noradrenaline reuptake inhibitor, was approved by the FDA on January 14th, 2009, for the treatment of fibromyalgia. ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn1000233
更新日期:2010-05-19 00:00:00
abstract::Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or ago...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn200128x
更新日期:2012-03-21 00:00:00
abstract::Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00120
更新日期:2016-08-17 00:00:00
abstract::Intra- and extraneuronal deposition of amyloid β (Aβ) peptides have been linked to Alzheimer's disease (AD). While both intra- and extraneuronal Aβ deposits affect neuronal cell viability, the molecular mechanism by which these Aβ structures, especially when intraneuronal, do so is still not entirely understood. This ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00491
更新日期:2019-03-20 00:00:00
abstract::The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with estrogens in protection of primary rat neurons against oxygen-glucose deprivation (OGD). Structure-activity relationships for neuroprotection were determined for a family of BT-SERMs displaying a spectrum of ERα and ERβ binding affinity and agon...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn100106a
更新日期:2011-05-18 00:00:00
abstract::Glycans are intimately involved in several facets of neuronal development and neuropathology. However, the metabolic labeling of surface glycans in primary neurons is a difficult task because of the neurotoxicity of unnatural monosaccharides that are used as a metabolic precursor, hindering the progress of metabolic e...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00300
更新日期:2017-12-20 00:00:00
abstract::Neurotrophins, as important regulators of neural development, function, and survival, have a therapeutic potential to repair damaged neurons. However, a controlled delivery of therapeutic molecules to injured tissue remains one of the greatest challenges facing the translation of novel drug therapeutics field. This st...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400080h
更新日期:2013-09-18 00:00:00
abstract::The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system,...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.9b00041
更新日期:2019-05-15 00:00:00
abstract::Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt...
journal_title:ACS chemical neuroscience
pub_type: 信件
doi:10.1021/cn100031t
更新日期:2010-07-21 00:00:00
abstract::Humanin (HN), a 24-amino acid bioactive peptide, has been shown to increase cell survival of neurons after exposure to Aβ and NMDA-induced toxicity and thus could be beneficial in the treatment of Alzheimer's disease (AD). The neuroprotection by HN is reported to be primarily through its agonist binding properties to ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00350
更新日期:2018-03-21 00:00:00
abstract::The delivery of specific genes into neurons offers a potent approach for treatment of diseases as well as for the study of neuronal cell biology. Here we investigated the capabilities of cationic amino acid based lipid assemblies to act as nonviral gene delivery vectors in primary cultured neurons. An arginine-based l...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400036j
更新日期:2013-12-18 00:00:00
abstract::The present experiments employed in vivo microdialysis to characterize the effects of commonly used endocannabinoid clearance inhibitors on basal and depolarization-induced alterations in interstitial endocannabinoid levels in the nucleus accumbens of rat brain. Compounds targeting the putative endocannabinoid transpo...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn300036b
更新日期:2012-05-16 00:00:00
abstract::Nowadays there are at present no efficient therapies for spinal cord injury (SCI), and new approaches have to be proposed. Recently, a new regenerative medicine strategy has been suggested using smart biomaterials able to carry and deliver cells and/or drugs in the damaged spinal cord. Among the wide field of emerging...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn200030w
更新日期:2011-07-20 00:00:00
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400106n
更新日期:2013-10-16 00:00:00
abstract::Glioblastoma multiforme, a type of deadly brain cancer, originates most commonly from astrocytes found in the brain. Current multimodal treatments for glioblastoma minimally increase life expectancy, but significant advancements in prognosis have not been made in the past few decades. Here we investigate cellular repr...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00365
更新日期:2018-12-19 00:00:00
abstract::Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and their effects on SOD1 aggregation remain unclear. This paper...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00086
更新日期:2018-07-18 00:00:00
abstract::The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer'...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00014
更新日期:2017-07-19 00:00:00
abstract::The lower efficacy of opioids in neuropathic pain may be due to the increased activity of pronociceptive systems such as substance P. We present evidence to support this hypothesis in this work from the spinal cord in a neuropathic pain model in mice. Biochemical analysis confirmed the elevated mRNA and protein level ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00226
更新日期:2017-10-18 00:00:00
abstract::The permeation of the potassium ion (K+) through the selectivity filter (SF) of the large conductance Ca2+-activated potassium (Slo1) channel remains an interesting question to study. Although the mode of K+ entering and leaving the SF has been revealed, the mechanism of K+ passing through the SF is still not clear. I...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00215
更新日期:2019-08-21 00:00:00
abstract::The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00018
更新日期:2017-03-15 00:00:00
abstract::Modulation of the neuropeptide S (NPS) system has been linked to a variety of CNS disorders such as panic disorder, anxiety, sleeping disorders, asthma, obesity, PTSD, and substance abuse. In this study, a series of diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-ones were synthesized and evaluated for antagonist ac...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500113c
更新日期:2014-08-20 00:00:00
abstract::Tau proteins are hyperphosphorylated at common sites in their N- and C-terminal domains in at least three neurodegenerative diseases, Parkinson, dementia with Lewy bodies, and Alzheimer's, suggesting specific pathology but general mechanism. Full-length human tau filament comprises a rigid core and a two-layered fuzzy...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00294
更新日期:2016-05-18 00:00:00