Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases

Rauf, Abdur; Badoni, Himani; Abu-Izneid, Tareq; Olatunde, Ahmed; Rahman, Md. Mominur; Painuli, Sakshi; Semwal, Prabhakar; Wilairatana, Polrat; Mubarak, Mohammad S.

doi:10.3390/molecules27103194

Cited by 139 publications

(74 citation statements)

References 244 publications

(298 reference statements)

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“…SIRT1 is a class III histone deacetylase that regulates various cellular functions, including oxidative stress, inflammation, energy metabolism, DNA damage repair, and cell death [ 63 , 64 ]. Increasing evidence suggests that neuroinflammation is closely associated with the pathogenesis of several neuronal diseases [ 65 , 66 ]. Extensive studies have demonstrated that SIRT1 has a neuroprotective effect on neuroinflammation-related diseases.…”

Section: Discussionmentioning

confidence: 99%

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

Yuan

Zhao

Shen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a regulated cell death that characterizes the lethal lipid peroxidation and iron overload, which may contribute to early brain injury (EBI) pathogenesis after subarachnoid hemorrhage (SAH). Although Sirtuin 1 (SIRT1), a class III histone deacetylase, has been proved to have endogenous neuroprotective effects on the EBI following SAH, the role of SIRT1 in ferroptosis has not been studied. Hence, we designed the current study to determine the role of ferroptosis in the EBI and explore the correlation between SIRT1 and ferroptosis after SAH. The pathways of ferroptosis were examined after experimental SAH in vivo (prechiasmatic cistern injection mouse model) and in HT-22 cells stimulated by oxyhemoglobin (oxyHb) in vitro. Then, ferrostatin-1 (Fer-1) was used further to determine the role of ferroptosis in EBI. Finally, we explored the correlation between SIRT1 and ferroptosis via regulating the expression of SIRT1 by resveratrol (RSV) and selisistat (SEL). Our results showed that ferroptosis was involved in the pathogenesis of EBI after SAH through multiple pathways, including acyl-CoA synthetase long-chain family member 4 (ACSL4) activation, iron metabolism disturbance, and the downregulation of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Inhibition of ferroptosis by Fer-1 significantly alleviated oxidative stress-mediated brain injury. SIRT1 activation could suppress SAH-induced ferroptosis by upregulating the expression of GPX4 and FSP1. Therefore, ferroptosis could be a potential therapeutic target for SAH, and SIRT1 activation is a promising method to inhibit ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

Yuan

Zhao

Shen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…However, it is worth mentioning that many challenging disorders are associated with a variety of objective proteins [ 32 , 33 , 34 ]. Furthermore, due to certain medicines having “poly-pharmacological” characteristics, unanticipated drug functionalities resulting from off-targets that are uncontrolled and unavoidable can lead to unpleasant side effects [ 7 , 35 , 36 , 37 , 38 , 39 ]. Sildenafil (Viagra), for example, is currently used to treat erectile dysfunction in men but was primarily designed for the treatment of angina [ 40 ].…”

Section: Anticancer Drug Target Predictionmentioning

confidence: 99%

Emerging Promise of Computational Techniques in Anti-Cancer Research: At a Glance

et al. 2022

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Research on the immune system and cancer has led to the development of new medicines that enable the former to attack cancer cells. Drugs that specifically target and destroy cancer cells are on the horizon; there are also drugs that use specific signals to stop cancer cells multiplying. Machine learning algorithms can significantly support and increase the rate of research on complicated diseases to help find new remedies. One area of medical study that could greatly benefit from machine learning algorithms is the exploration of cancer genomes and the discovery of the best treatment protocols for different subtypes of the disease. However, developing a new drug is time-consuming, complicated, dangerous, and costly. Traditional drug production can take up to 15 years, costing over USD 1 billion. Therefore, computer-aided drug design (CADD) has emerged as a powerful and promising technology to develop quicker, cheaper, and more efficient designs. Many new technologies and methods have been introduced to enhance drug development productivity and analytical methodologies, and they have become a crucial part of many drug discovery programs; many scanning programs, for example, use ligand screening and structural virtual screening techniques from hit detection to optimization. In this review, we examined various types of computational methods focusing on anticancer drugs. Machine-based learning in basic and translational cancer research that could reach new levels of personalized medicine marked by speedy and advanced data analysis is still beyond reach. Ending cancer as we know it means ensuring that every patient has access to safe and effective therapies. Recent developments in computational drug discovery technologies have had a large and remarkable impact on the design of anticancer drugs and have also yielded useful insights into the field of cancer therapy. With an emphasis on anticancer medications, we covered the various components of computer-aided drug development in this paper. Transcriptomics, toxicogenomics, functional genomics, and biological networks are only a few examples of the bioinformatics techniques used to forecast anticancer medications and treatment combinations based on multi-omics data. We believe that a general review of the databases that are now available and the computational techniques used today will be beneficial for the creation of new cancer treatment approaches.

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“…Neuroinflammation is the complex innate immune response (sometimes adaptive) against internal or external agents, aiming to resist or resolve harmful threats to restore homeostasis [ 4 , 15 , 16 ]. Two glial cells, microglia and astrocytes, are cornerstones in this process as they restrain infection and eliminate pathogens, cell debris, and misfolded proteins.…”

Section: Glial Cell-mediated Neuroinflammationmentioning

confidence: 99%

“…The cornerstones of remyelination are glial cell-mediated neuroinflammation, the over-production of mitochondrial reactive oxygen species (ROS), and mitochondrial dysfunction. Importantly, these features occur in other neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [ 4 ]. Another aspect common to neurodegenerative and/or neurological disorders, including MS, is the deficiency of the Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathway, a critical antioxidant transcription factor that prevents mitochondrial failure, oxidative stress, and neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

Neurodegeneration in Multiple Sclerosis: The Role of Nrf2-Dependent Pathways

et al. 2022

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Multiple sclerosis (MS) encompasses a chronic, irreversible, and predominantly immune-mediated disease of the central nervous system that leads to axonal degeneration, neuronal death, and several neurological symptoms. Although various immune therapies have reduced relapse rates and the severity of symptoms in relapsing-remitting MS, there is still no cure for this devastating disease. In this brief review, we discuss the role of mitochondria dysfunction in the progression of MS, focused on the possible role of Nrf2 signaling in orchestrating the impairment of critical cellular and molecular aspects such as reactive oxygen species (ROS) management, under neuroinflammation and neurodegeneration in MS. In this scenario, we propose a new potential downstream signaling of Nrf2 pathway, namely the opening of hemichannels and pannexons. These large-pore channels are known to modulate glial/neuronal function and ROS production as they are permeable to extracellular Ca2+ and release potentially harmful transmitters to the synaptic cleft. In this way, the Nrf2 dysfunction impairs not only the bioenergetics and metabolic properties of glial cells but also the proper antioxidant defense and energy supply that they provide to neurons.

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Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases

Cited by 139 publications

References 244 publications

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

Emerging Promise of Computational Techniques in Anti-Cancer Research: At a Glance

Neurodegeneration in Multiple Sclerosis: The Role of Nrf2-Dependent Pathways

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