scholarly journals Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients

Author(s):  
Mahtab Shahriari-Felordi ◽  
Hani Keshavarz Alikhani ◽  
Seyed-Mohammad Reza Hashemian ◽  
Moustapha Hassan ◽  
Massoud Vosough
Keyword(s):  
2021 ◽  
Author(s):  
Fathima Hajee Basha ◽  
S. Hemalatha

Abstract Neurodegeneration may be defined as a clinical condition wherein neurons gradually lose their structural integrity, viability, functional abilities and the damage inflicted upon the neurons is often irreversible. The number of elderly patients suffering from Neurodegenerative disorders is expected to rise tremendously over the next couple of years. Thus, there is an urgent need to delve into and study the underlying cause and mechanisms, so that we may be able to develop more effective therapeutic strategies and drugs and better understand the origin and progression of the disease.The various mechanisms that have been observed to contribute to neurodegeneration include aggregation and accumulation of misfolded proteins, impaired autophagy, oxidative damage, neuroinflammation, mitochondrial defects, increased SUMOylation of proteins, impaired UPR pathways, disruption of axonal transport.Melatonin, a neurohormone is involved in a variety of functions including scavenging free radicals, synchronizing the circadian rhythm, mitigating immune response.Melatonin has shown to modulate the UPR pathway ,antioxidant pathway through Nrf2 and inflammatory pathway through NFκB. The study aims to determine the efficacy of melatonin on neurodegeneration mediated by ER stress, inflammation and oxidative damage through in silico approaches. The molecular targets chosen were ATF6, XBP1, PERK, Nrf2, NFκB and they were docked against melatonin. Additionally various physiochemical analysis such as ADME were also carried out to determine its drug ability. The findings were that melatonin not only shows excellent interactions with the targets but also possess drug-like physicochemical properties that makes it a valuable choice for the treatment of neurodegenerative disorders.


2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
P De Medina ◽  
S Genovese ◽  
M Pailasse ◽  
S Silvente-Poirot ◽  
M Curini ◽  
...  

2013 ◽  
Vol 8 (S 01) ◽  
Author(s):  
S Behrendt ◽  
D Löffler ◽  
R Tauscher ◽  
A Körner

2013 ◽  
Vol 8 (S 01) ◽  
Author(s):  
D Sommerweiss ◽  
T Gorski ◽  
S Laue ◽  
S Schuster ◽  
A Garten ◽  
...  
Keyword(s):  

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
C Funke ◽  
J Hübener ◽  
H Wolburg ◽  
T Schmidt ◽  
H Toresson ◽  
...  

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