5-lipoxygenase pathway and its downstream cysteinyl leukotrienes as potential therapeutic targets for Alzheimer’s disease

Chen, Fang; Ghosh, Arijit; Lin, Jingran; Zhang, Chunteng; Pan, Yanhong; Thakur, Abhimanyu; Singh, Kunal Kumar; Hong, Hao; Tang, Shuming

doi:10.1016/j.bbi.2020.03.022

Cited by 37 publications

(21 citation statements)

References 116 publications

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“…Research manifested that LTA4, as an active lipid, critically related to in ammation. Currently, ALOX5 has been reported to be involved in the pathogenesis of multiple diseases, such as asthma, cardiovascular diseases, multiple sclerosis, tumors and allergic diseases, etc [59][60][61][62][63]. Our study further demonstrated that ALOX5 could dramatically reverse miR-183-medaited proliferation and apoptosis of HL-7702 cells with I/R injury, indicating that miR-183 could notably attenuate liver I/R injury by targeting ALOX5.…”

Section: Discussionsupporting

confidence: 60%

“…ALOX5 gene, which is located on chromosome 10q11.2, can encode 5-lipoxygenase (5-LO) containing 673 amino acids [58]. After activation, ALOX5 can be transferred to the nuclear membrane and interact with ALOX5 activated protein (FLAP), then converts AA to leukotriene and 5-hydroperoxy-eicostetraeoic acid (5-HpETE), which is further metabolized into leukotriene A4 (LTA4), LTB4 and LTC4 [59]. Research manifested that LTA4, as an active lipid, critically related to in ammation.…”

Section: Discussionmentioning

confidence: 99%

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Exosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 axisExosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 Axis

Gong¹,

Dai²,

Liu³

et al. 2021

Preprint

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BackgroundIschemia-reperfusion (I/R) injury a crucial factor causing liver injury in clinic. Recent research confirmed that human adipose-derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of ADSCs in the treatment of liver injury remains unclear.MethodsCharacteristics of ADSCs were first identified, and exosomes from miR-183-overexpressed ADSCs were isolated and identified. And the function and mechanism of microRNA-183 (miR-183) and arachidonate 5-lipoxygenase (ALOX5) were monitored through biological experiments in HL-7702 cells with I/R injury or I/R rats. ResultsWe proved that inhibition of exosomes from the identified ADSCs prevented proliferation, induced apoptosis and downregulated miR-183 in HL-7702 cells with I/R injury, while exosomes derived from ADSCs played an opposite role on the proliferation and apoptosis of HL-7702 cells with I/R injury in comparison with exosome inhibitors by upregulating miR-183. Meanwhile, the effect of miR-183 alone was similar to that of exosomes derived from ADSCs. Besides, ALOX5, as a target gene of miR-183, was involved in the related functions of miR-183. Moreover, in vivo experiments further confirmed miR-183 or exosomes from ADSCs also could improve liver injury of rats and downregulate MAPK and NF-κB pathways.ConclusionAll these findings testified that exosomes derived from miR-183-overexpressing ADSCs have a significant protective effect on hepatic I/R injury by regulating miR-183/ALOX5 axis, which might provide therapeutic strategy for liver injury.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 axisExosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 Axis

Gong¹,

Dai²,

Liu³

et al. 2021

Preprint

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“…LTD 4 directly upregulates beta-secretase (BACE)1, the enzyme responsible for β-amyloid production in neurons [ 78 ]. Similar expression of CysLT receptors on astrocytes and microglia is observed in AD as in PD mouse models, but upregulation of these cells is observed in the hippocampus and cortex where AD pathology is most abundant [ 79 ].…”

Section: Leukotriene Signaling Pathwaymentioning

confidence: 99%

Potential Effects of Leukotriene Receptor Antagonist Montelukast in Treatment of Neuroinflammation in Parkinson’s Disease

Wallin

Svenningsson

2021

IJMS

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Parkinson’s disease (PD) is a neurodegenerative disorder where misfolded alpha-synuclein-enriched aggregates called Lewy bodies are central in pathogenesis. No neuroprotective or disease-modifying treatments are currently available. Parkinson’s disease is considered a multifactorial disease and evidence from multiple patient studies and animal models has shown a significant immune component during the course of the disease, highlighting immunomodulation as a potential treatment strategy. The immune changes occur centrally, involving microglia and astrocytes but also peripherally with changes to the innate and adaptive immune system. Here, we review current understanding of different components of the PD immune response with a particular emphasis on the leukotriene pathway. We will also describe evidence of montelukast, a leukotriene receptor antagonist, as a possible anti-inflammatory treatment for PD.

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“…It adversely affects the planet and is toxic to its inhabitants. Pollution damages health at all ages and even in utero [37][38]. The lungs are the primary victims of air pollution causing many diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and various respiratory infections.…”

Section: Impact On the Environmentmentioning

confidence: 99%

An overview of the implications of covid-19 on economy, education and mental health

Khan¹,

Ahmed²,

Anwar³

2021

World J. Adv. Res. Rev.

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Coronavirus 2019 (COVID-19), a viral infection, has taken over the world. The infection was declared as a pandemic and a Public Health Emergency of International Concern in January 2020. Since then there have been lockdowns in numerous countries, causing multiple complications in not only the health sector but also in various aspects of life. COVID-19 has grid-locked the economy and is expected to lead to an economic crisis in the near future. The education system is also affected as examinations have been cancelled and classes are being given online which has decreased the quality. The lockdown has had a negative impact on human psychology. Amidst these circumstances, there are steps being taken to cope with these critical situations. Since the outbreak of COVID-19 pandemic, a huge amount of formal and informal studies have appeared in literature. Given the diversity of media choices, the emerging knowledge has reached across the globe within very limited time. These studies, individually, have focused on almost all the aspects affected by the pandemic, like economy, healthcare, tourism, education etc. This study by the authors provides a simplified overview of impacts of COVID-19 noted by various research studies. It is a useful concise account of COVID-19 effects in one-reading covering aspects like effects on healthcare & healthcare workers, human behavior & mental health, tourism, pollution and education.

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5-lipoxygenase pathway and its downstream cysteinyl leukotrienes as potential therapeutic targets for Alzheimer’s disease

Cited by 37 publications

References 116 publications

Potential Effects of Leukotriene Receptor Antagonist Montelukast in Treatment of Neuroinflammation in Parkinson’s Disease

An overview of the implications of covid-19 on economy, education and mental health

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