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Genes & Diseases 2024年第4期11卷 106-108页

作者： Gloria Garav.to-De Egea Alex Dominguez-v.rgas Jorg e l.v.lez Gustav. Aroca Luis Fagng Elkin Nav.rro-Quiroz Zilac Espitaleta Kenny Del Toro-Camargo Leticia martinez-Ariza Tatiana Gonzalez-v.rgas Susana Garcia Mauricio Arcos-Burgos Eduardo Egea Univ.rsidad del Norte Division Ciencias de la SaludBarranquillaColombia Univ.rsidad Simon Boliv.r Facultad de Ciencias de la SaludBarranquillaColombia Clinica de la Costa Grupo de Investigacion en NefrologiaBarranquillaColombia Univ.rsidad de Antioquia Grupo de Investigacion en Psiquiatria(GIPSI)Departamento de PsiquiatriaInstituto de Investigaciones MedicasFacultad de MedicinaMedellinColombia

Genome-wide association studies(GWASs)hav. identified hundreds of loci across the human genome conferring susceptibility to autoimmune diseases(AIDs),some of which are shared between more than two ***,this univ.riate ... 详细信息

关键词： susceptibility diseases diabetes

MicroRNAs as biomarkers in glaucoma and potential therapeutic targets

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Neural Regeneration Research 2022年第11期17卷 2368-2375页

作者： Bridget martinez Philip v.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Glaucoma is a neurodegenerativ. disease in which optic nerv. damage and v.sual field defects *** is a leading cause of irrev.rsible *** pathogenesis is largely unknown although sev.ral risk factors hav. been identified,with an increase in intraocular pressure being the main *** of intraocular pressure is the only treatment ***-angle glaucoma is the most common form of the condition,accounting for~90%of all cases of glaucoma,with primary open-angle glaucoma and exfoliation glaucoma being the most frequent *** are strong indications that microRNAs play important roles in the pathogenesis of primary open-angle *** of the recent studies rev.ewed had performed microRNA profiling in aqueous humor from glaucoma patients compared to controls who were chiefly cataract patients.A v.ry large number of microRNAs were dysregulated but with limited ov.rlap between indiv.dual *** in aqueous humor that could be possible targets for therapeutic interv.ntion are miR-143-3p,miR-125b-5p,and *** ov. rlap of findings occurred within the dysregulated miRNAs for blood plasma,blood serum,peripheral blood mononuclear cells,and tears of primary open-angle glaucoma *** ral impo rtant limitations were identified in these *** studies are warranted of mic roRNA expression in aqueous humor and blood samples of primary open-angle glaucoma patients in the early stages of the disease so that v.lidated biomarkers can be identified and treatment *** addition,whether modifying the lev.ls of specific microRNAs in aqueous humor or tears has a beneficial effect on intraocular pressure and ophthalmic examination of the eyes should be inv.stigated using suitable animal models of glaucoma.

关键词： aqueous humor biomarkers blood plasma blood serum glaucoma intraocular pressure microRNA peripheral blood mononuclear cells tears therapeutic targets

MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第7期17卷 1412-1422页

作者： Bridget martinez Philip v.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Frontotemporal lobar degeneration describes a group of progressiv. brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal *** lobar degeneration is considered to be equiv.lent to frontotemporal *** dementia is characterized by progressiv. impairments in behav.or,executiv. function,and *** are two main clinical subtypes:behav.oral-v.riant frontotemporal dementia and primary progressiv. *** early diagnosis of frontotemporal dementia is critical for dev.loping management strategies and interv.ntions for these *** v.lidated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to ov.rlap with a range of neurologic and psychiatric *** the studies rev.ewed a v.ry large number of microRNAs were found to be dysregulated but with limited ov.rlap between indiv.dual *** of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral ***,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behav.oral-v.riant frontotemporal dementia from healthy *** of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectiv.ly,from healthy *** strong miRNA biofluid biomarker contenders for behav.oral-v.riant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal *** miRNAs were identified able to distinguish between behav.oral-v.riant frontotemporal dementia and primary progressiv. aphasia *** studies are

关键词： Alzheimer’s disease amyotrophic lateral sclerosis behav.oral v.riant biomarker blood plasma blood serum brain cerebrospinal fluid cortical tissue frontotemporal dementia frontotemporal lobar degeneration microRNA primary progressiv. aphasia

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

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Neural Regeneration Research 2023年第10期18卷 2108-2118页

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitiv. impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nerv.us system and play important roles in the pathogenesis of sev.ral neurological disorders, including epilepsy. A v.riety of animals(mostly mice and rats) hav. been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies rev.ewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Ov.rexpression of miR-137 and miR-219 decreased seizure sev.rity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positiv. influence on seizure behav.or. In the rat studies, ov.rexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positiv. effect on seizure behav.or and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activ.ty in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys giv.n intrahippocampal injections of kainic acid.

关键词： epilepsy experimental models microRNA mouse rat seizures therapeutic targets

MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

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Neural Regeneration Research 2023年第4期18卷 716-726页

作者： Bridget martinez Philip v.Peplow Department of Pharmacology University of Nevada-RenoRenoNEVUSA Department of Medicine University of Nevada-RenoRenoNEVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or inv.lv.ng mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic *** lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain *** of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain *** or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be *** possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro *** of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some ov.rlap between indiv.dual studies that could serv. as potential *** example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood *** adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood ***,in many of the studies inv.lv.ng patients who receiv. one or sev.ral anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely *** studies are warranted with children with temporal lobe epilepsy and consideration should be giv.n to utilizing mouse or rat and non-human primate models of temporal lobe epil

关键词： adults biomarkers blood plasma blood serum children hippocampal tissue mesial temporal lobe epilepsy microRNA temporal cortical tissue temporal lobe epilepsy

Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

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Neural Regeneration Research 2021年第11期16卷 2159-2169页

作者： Bridget martinez Philip v.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A rev.ew of recent animal models of Huntington’s disease showed many microRNAs had altered expression lev.ls in the striatum and cerebral cortex,and which were mostly *** the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been prev.ously found in Huntington’s disease *** the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,ov.rexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein lev.l,lowered the mutant huntingtin aggregates in striatum and cortex,and improv.d performance in behav.oral *** performance in behav.oral tests also occurred with ov.rexpression of miR-132 and *** the animal cell models,ov.rexpression of miR-22 increased the v.ability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μ***,ov.rexpression of miR-22 enhanced the surv.v.l of rat primary striatal neurons treated with 3-nitropropionic *** expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 *** studies with animal models of Huntington’s disease are warranted to v.lidate these findings and identify specific microRNAs whose ov.rexpression inhibits the production of mutant huntingtin protein and other harmful processes and may prov.de a more effectiv. means of treating Huntington’s disease in patients and slowing its progression.

关键词： animal model cerebral cortex huntingtin Huntington’s disease microRNA neurodegeneration striatum therapeutic strategies

Biomaterial and tissue-engineering strategies for the treatment of brain neurodegeneration

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Neural Regeneration Research 2022年第10期17卷 2108-2116页

作者： Bridget martinez Philip v.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

The incidence of neurodegenerativ. diseases is increasing due to changing age demographics and the incidence of sports-related traumatic brain injury is tending to increase ov.r *** approv.d medicines for neurodegenerativ. diseases only temporarily reduce the symptoms but cannot cure or delay disease *** transplantation strategies offer an alternativ. approach to facilitating central nerv.us system repair,but efficacy is limited by low in v.v. surv.v.l rates of cells that are injected in *** cells that are attached to or encapsulated within a suitable biomaterial construct has the adv.ntage of enhancing cell surv.v.l in v.v..A v.riety of biomaterials hav. been used to make constructs in different types that included nanoparticles,nanotubes,microspheres,microscale fibrous scaffolds,as well as scaffolds made of gels and in the form of *** these,Tween 80-methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid)nanoparticles loaded with rhynchophylline had higher transport across a blood-brain barrier model and decreased cell death in an in v.tro model of Alzheimer’s disease than rhynchophylline or untreated nanoparticles with *** an in v.tro model of Parkinson’s disease,trans-activ.ting transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin had a similar protectiv. ability as free non-Fe hemin.A positiv. effect on neuron surv.v.l in sev.ral in v.v. models of Parkinson’s disease was associated with the use of biomaterial constructs such as trans-activ.ting transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin,carbon nanotubes with olfactory bulb stem cells,poly(lactic-co-glycolic acid)microspheres with attached DI-MIAMI cells,v.ntral midbrain neurons mixed with short fibers of poly-(L-lactic acid

关键词： Alzheimer’s disease biomaterial cell transplantation neurodegeneration neurodegenerativ. disease Parkinson’s disease tissue-engineering traumatic brain injury

MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

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Neural Regeneration Research 2022年第4期17卷 728-740页

A rev.ew of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered lev.ls of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly *** the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days v..108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improv.d muscle strength,reduced neuromuscular junction degeneration,and tended to improv. motor neuron surv.v.l in the SOD1(G93 A)mouse *** of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improv. lifespan in males and increase muscle strength in SOD1(G93 A)*** of members of mi R-17~92 cluster improv.d motor neuron surv.v.l in SOD1(G93 A)*** with an artificial mi RNA designed to target h SOD1 increased lifespan and improv.d muscle strength in SOD1(G93 A)*** studies with animal models of amyotrophic lateral sclerosis are warranted to v.lidate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improv.d muscle strength,reduced neuromuscular junction degeneration,and improv.d motor neuron surv.v.l in SOD1(G93 A)animals.

关键词： amyotrophic lateral sclerosis animal model brain brainstem microRNA motor neuron degeneration spinal cord therapeutic approaches

Blood microRNAs as potential diagnostic markers for hemorrhagic stroke

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Neural Regeneration Research 2017年第1期12卷 13-18页

作者： Bridget martinez Philip v.Peplow Department of Molecular and Cellular Biology University of California Department of Anatomy University of Otago

Proper medical treatment of a stroke v.ctim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography（CT） or magnetic resonance imaging（MRI） scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic *** rev.ew has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal *** also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage *** miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic *** or increased miRNA lev.ls may be needed either as prev.ntion or treatment of *** in v.v. of miR-130 a inhibitor or miRNA mimic（miR-367,miR-223） in an intracerebral hemorrhage animal model improv.d neurological outcomes.

关键词： blood microRNAs diagnostic biomarkers hemorrhagic stroke human patients rat and mouse models

MicroRNAs as diagnostic and therapeutic tools for Alzheimer's disease: adv.nces and limitations

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Neural Regeneration Research 2019年第2期14卷 242-255页

作者： Bridget martinez Philip v.Peplow Department of Molecular & Cellular Biology University of CaliforniaMerced CA USA Department of Medicine St.Georges University School of MedicineGrenada Department of Physics and Engineering Los Alamos National Laboratory Department of Anatomy University of Otago

Alzheimer's disease(AD) is the most common age-related, progressiv. neurodegenerativ. disease. It is characterized by memory loss and cognitiv. decline and responsible for most cases of dementia in the elderly. Late-onset or sporadic AD accounts for > 95% of cases, with age at onset > 65 years. Currently there are no drugs or other therapeutic agents av.ilable to prev.nt or delay the progression of AD. The cellular and molecular changes occurring in the brains of indiv.duals with AD include accumulation of β-amyloid peptide and hyperphosphorylated tau protein, decrease of acetylcholine neurotransmitter, inflammation, and oxidativ. stress. Aggregation of β-amyloid peptide in extracellular plaques and the hyperphosphorylated tau protein in intracellular neurofibrillary tangles are characteristic of AD. A major challenge is identifying molecular biomarkers of the early-stage AD in patients as most studies hav. been performed with blood or brain tissue samples(postmortem) at late-stage AD. Subjects with mild cognitiv. impairment almost always hav. the neuropathologic features of AD with about 50% of mild cognitiv. impairment patients progressing to AD. They could prov.de important information about AD pathomechanism and potentially also highlight minimally or noninv.siv., easy-to-access biomarkers. MicroRNAs are dysregulated in AD, and may facilitate the early detection of the disease and potentially the continual monitoring of disease progression and allow therapeutic interv.ntions to be ev.luated. Four recent rev.ews hav. been published of microRNAs in AD, each of which identified areas of weakness or limitations in the reported studies. Importantly, studies in the last three years hav. shown considerable progress in ov.rcoming some of these limitations and identifying specific microRNAs as biomarkers for AD and mild cognitiv. impairment. Further large-scale human studies are warranted with less disparity in the study populations, and using an appropriate method to v.

关键词： Alzheimer's disease mild cognitiv. impairment microRNAs biomarkers blood brain tissue cerebrospinal fluid humans animal models