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Exploiting fly models to investigate rare human neurological disorders

Neural Regeneration research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung department of Neurology Houston Methodist Research InstituteHoustonTXUSA department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

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Status and prospects for symmetric organic redox flow batteries

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Journal of Energy Chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan C.Adam Dyker department of Chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha J.Holdsworth Alistair J.Gunn Laura Bennet Hamid Abbasi Mātai Medical research Institute Tairāwhiti GisborneNew Zealand department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Astrocytes integrate time and space

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Neural Regeneration research 2025年第2期20卷 467-468页

作者： Justin Lines department of Biological Sciences Columbia UniversityNew YorkNYUSA

Astrocytes read and react to synaptic transmission through tripartite synapses,where the binding of neurotransmitters onto astrocytic receptors triggers an increase in intracellular *** investigations have revealed that astrocytes exhibit two distinct states of intracellular calcium activity:(1)graded subcellular localized clusters with independently active microdomains,likely influenced by nearby synaptic events,and(2)whole-cell astrocyte calcium surges,believed to result from the coordinated activation of multiple ***,astrocyte calcium responses are not solely graded;instead,a spatial threshold of intracellular calcium activity can be overcome to elicit an astrocyte calcium *** these calcium responses,in turn,initiate downstream signaling pathways capable of modifying synaptic communication and overall network *** summary,astrocytes can function as integrators of local synaptic events,actively contributing to information processing within the brain.

关键词： graded integrate instead

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Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama Center for Brain research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky Center for Brain research and department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

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Alpha-synuclein in mitochondrial dysfunction:opportunities or obstacles

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Neural Regeneration research 2025年第1期20卷 197-198页

作者： Shermali Gunawardena department of Biological Sciences The State University of New York at BuffaloBuffaloNYUSA

Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still *** notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is *** date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.

关键词： dysfunction homeostasis Alpha

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MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration research 2025年第7期20卷 1957-1970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

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

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Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

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Neural Regeneration research 2025年第10期20卷 2776-2786页

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear *** of the studies involved children and the study cohorts were largely *** of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA *** five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to *** microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of *** important limitations were identified in the studies reviewed,and need to be taken into account in future *** studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

关键词： autism spectrum disorder biomarker blood cells blood plasma blood serum diagnosis microRNA peripheral blood mononuclear cells serum neural cell adhesion molecule L1-captured extracellular vesicles whole blood

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration research 2025年第6期20卷 1681-1695页

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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