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Regulation of enolase activation to promote neural protection and regeneration in spinal cord injury

Neural Regeneration Research 2023年第7期18卷 1457-1462页

作者： Hannah MMcCoy Rachel Polcyn Naren LBanik azizul haque Department of Microbiology and Immunology Medical University of South CarolinaCharlestonSCUSA Department of Neurosurgery Medical University of South CarolinaCharlestonSCUSA Ralph H.Johnson Veterans Administration Medical Center CharlestonSCUSA

Spinal cord injury(SCI)is a debilitating condition characterized by damage to the spinal cord resulting in loss of function,mobility,and sensation with no U.S.Food and Drug Administration-approved cure.Enolase,a multifunctional glycolytic enzyme upregulated after SCI,promotes pro-and anti-inflammatory events and regulates functional recovery in SCI.Enolase is normally expressed in the cytosol,but the expression is upregulated at the cell surface following cellular injury,promoting glial cell activation and signal transduction pathway activation.SCI-induced microglia activation triggers pro-inflammatory mediators at the injury site,activating other immune cells and metabolic events,i.e.,Rho-associated kinase,contributing to the neuroinflammation found in SCI.Enolase surface expression also activates cathepsin X,resulting in cleavage of the C-terminal end of neuron-specific enolase(NSE)and non-neuronal enolase(NNE).Fully functional enolase is necessary as NSE/NNE C-terminal proteins activate many neurotrophic processes,i.e.,the plasminogen activation system,phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B,and mitogen-activated protein kinase/extracellular signal-regulated kinase.Studies here suggest an enolase inhibitor,ENOblock,attenuates the activation of Rho-associated kinase,which may decrease glial cell activation and promote functional recovery following SCI.Also,ENOblock inhibits cathepsin X,which may help prevent the cleavage of the neurotrophic C-terminal protein allowing full plasminogen activation and phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase activity.The combined NSE/cathepsin X inhibition may serve as a potential therapeutic strategy for preventing neuroinflammation/degeneration and promoting neural cell regeneration and recovery following SCI.The role of cell membrane-expressed enolase and associated metabolic events should be investigated to determine if the same strategies can be applied to other neurodegenerative diseases.Hence,this review discus

关键词： cathepsin X ENOblock enolase glia mitogen-activated protein kinase/extracellular signal-regulated kinase neurodegeneration neuroinflammation phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B Rho-associated protein kinase spinal cord injury

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Clemastine in remyelination and protection of neurons and skeletal muscle after spinal cord injury

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Neural Regeneration Research 2023年第5期18卷 940-946页

作者： Ali Myatich azizul haque Christopher Sole Naren L.Banik Department of Microbiology and Immunology Medical University of South CarolinaCharlestonSCUSA Department of Neurosurgery Medical University of South CarolinaCharlestonSCUSA Ralph H.Johnson Veterans Administration Medical Center CharlestonSCUSA Department of Health and Human Performance The CitadelCharlestonSCUSA

Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.

关键词： axonal damage clemastine myelination neuronal death oligodendrocytes skeletal muscle spinal cord injury

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Implications of enolase in the RANKL-mediated osteoclast activity following spinal cord injury

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BIOCELL 2021年第6期45卷 1453-1457页

作者： RAMSHA SHAMS NAREN LBANIK azizul haque Department of Microbiology and Immunology Medical University of South CarolinaCharlestonSC 29425USA Department of Neurosurgery Medical University of South CarolinaCharlestonSC 29425USA Ralph H.Johnson Veterans Administration Medical Center CharlestonSC 29401USA

Spinal Cord Injury(SCI)is a debilitating condition characterized by damage to the spinal cord,resulting in loss of function,mobility,and sensation.Although increasingly prevalent in the US,no FDA-approved therapy exists due to the unfortunate complexity of the condition,and the difficulties of SCI may be furthered by the development of SCI-related complications,such as osteoporosis.SCI demonstrates two crucial stages for consideration:the primary stage and the secondary stage.While the primary stage is suggested to be immediate and irreversible,the secondary stage is proposed as a promising window of opportunity for therapeutic intervention.Enolase,a metabolic enzyme upregulated after SCI,performs non-glycolytic functions,promoting inflammatory events via extracellular degradative actions and increased production of inflammatory cytokines and chemokines.Neuron-specific enolase(NSE)serves as a biomarker of functional damage to neurons following SCI,and the inhibition of NSE has been demonstrated to reduce signs of secondary injury of SCI and to ameliorate dysfunction.This Viewpoint article involves enolase activation in the regulation of RANK-RANKL pathway and summarizes succinctly the mechanisms influencing osteoclast-mediated resorption of bone in SCI.Our laboratory proposes that inhibition of enolase activation may reduce SCI-induced inflammatory response and decrease osteoclast activity,limiting the chances of skeletal tissue loss in SCI.

关键词： Enolase RANK RANKL Osteoporosis Neuronal death Spinal cord injury

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Neuron specific enolase is a potential target for regulating neuronal cell survival and death: implications in neurodegeneration and regeneration

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Neuroimmunology and Neuroinflammation 2017年第12期4卷 254-257页

作者： Rachel Polcyn Mollie Capone Azim Hossain Denise Matzelle Naren L.Banik azizul haque Department of Microbiology and Immunology Hollings Cancer CenterMedical University of South CarolinaCharlestonSC 29425USA Department of Neurosurgery Medical University of South CarolinaCharlestonSC 29425USA Ralph H.Johnson Veterans Administration Medical Center CharlestonSC 29401USA.

Enolase is a multifunctional enzyme primarily involved in catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate during glycolysis and the reverse reaction during gluconeogenesis[1-4].Though typically ... 详细信息

关键词： Neuron specific enolase potential target regulating neuronal cell survival

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Monkeypox virus(MPXV):A Brief account of global spread,epidemiology,virology,clinical features,pathogenesis,and therapeutic interventions

Infectious Medicine

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Infectious Medicine 2023年第4期2卷 262-272页

作者： Md Aminul Islam Jubayer Mumin Md Masudul haque Mdazizul haque Ahrar Khan Prosun Bhattacharya Md Atiqul haque Advanced Molecular Lab Department of MicrobiologyPresident Abdul Hamid Medical CollegeKarimganj 2310Bangladesh COVID-19 Diagnostic Lab Department of MicrobiologyNoakhali Science and Technology UniversityNoakhali 3814Bangladesh Department of Global Public Health Karolinska InstitutetSE-17177 StockholmSweden Department of Public Health North South UniversityDhaka 1229Bangladesh Department of Biochemistry and Molecular Biology Faculty of AgricultureHajee Mohammad Danesh Science and Technology UniversityDinajpur 5200Bangladesh Shandong Vocational Animal Science and Veterinary College Weifang 261061China COVID-19 Research@KTH Department of Sustainable DevelopmentEnvironmental Science and EngineeringKTH Royal Institute of TechnologySE-10044 StockholmSweden Key Laboratory of Animal Epidemiology and Zoonoses of Ministry of Agriculture College of Veterinary MedicineChina Agricultural UniversityBeijing 100019China Department of Microbiology Faculty of Veterinary and Animal ScienceHajee Mohammad Danesh Science and Technology UniversityDinajpur 5200Bangladesh

The largest monkeypox virus(MPXV)outbreak of the 21st century occurred in 2022,which caused epidemics in many countries.According to WHO,physical contact with infected persons,contaminated surfaces,or affected animals might be a source of this virus transmission.A febrile sickness including few symptoms found in MPX disease.Skin rash,lesions,fever,headache,fatigue,and muscle aches symptoms were observed commonly for this disease.Animal and in vitro,studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV.The first-generation vaccinia virus vaccine was developed in 1960,and it helped to protect against MPXV with its side effects.A second-generation vaccination with limitations was launched in 2000.However,the CDC advised vaccinations for risk groups in endemic countries,including positive patients and hospital employees.The JYNNEOS vaccine,administered in 2 doses,also provides protection from MPX.This article presents concisely the most recent findings regarding epidemiology,genomic transmission,signs and symptoms,pathogenesis,diagnosis,and therapeutic interventions for MPXV,which may be helpful to researchers and practitioners.WHO declared that MPX was no longer a global health emergency due to its declining case rate,and a number of countries have reported new incidences.Further research-based investigations must be carried out based on the 2022 outbreak.

关键词： Monkeypox(MPX) Monkeypox virus(MPXV) Epidemiology Zoonotic diseases Re-emerging viruses Genomic dissemination Vaccination and Treatment

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