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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Adding new dimension to non-directed C（sp3）–H functionalizations

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Science China Chemistry 2025年

作者： Konstantin p.Bryliakov Laboratory of Selective Oxidation Catalysis N.D.Zelinsky Institute of Organic Chemistry RAS

Aliphatic C–H groups are among the most abundant yet least reactive functional groups in organic molecules. Nature has evolved metalloenzymes such as those of the cytochrome p450 superfamily that efficiently activate individual tertiary（3） and secondary （2） C（sp3）–H bonds in complex molecules with the highest level of regio-and stereoselectivity [1], thus encouraging studies aimed at engineering artificial metalloenzymes for synthetic applications [2].

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

Synergistic effect of flavonoids combined with antivenom on neutralisation of Naja naja venom

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Asian pacific Journal of Tropical Biomedicine 2021年第7期11卷 298-307页

作者： Srimathi raghavan Gurunathan Jayaraman School of Biosciences and Technology Vellore Institute of TechnologyVellore 632014India

Objective:To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial ***:Synthetic flavonoids were assessed,either individually or in combination with antivenom,for their neutralization of phospholipase A_(2)(pLA_(2)),protease,antioxidant(DppH)assay and hemotoxic *** docking studies were performed to understand possible binding of flavonoids with Naja naja venom pLA_(2).In vivo studies were carried out to confirm the neutralisation effects using a mouse ***,inhibition of pLA_(2) was monitored using combinatorial ***:Among the flavonoids used,quercetin and naringenin inhibited pLA_(2)(56%and 45%),protease(71%and 64%),DppH scavenging(69.0%and 77.5%)and hemotoxic(70%)*** docking studies indicated that the flavonoids bind to the substrate-binding site of pLA_(2)(Cys44 and Tyr63).In vivo studies showed a reduction in the venom toxicity level in the presence of ***,combinatorial studies using the mixture of flavonoid and anti-venom revealed the possibility of synergistic effect(up to 32%enhancement)in neutralising the venom ***:These flavonoids can be used as additives for the treatment of snake bites,which may exert synergistic effects in combination with antivenom and decrease the post-therapeutic effects caused by excessive use of antivenom.

关键词： Flavonoid Anti-venom Snake bite Combinatorial Synergistic Naja naja

Withania somnifera: a pre-clinical study on neuroregenerative therapy for stroke

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Neural Regeneration Research 2015年第2期10卷 183-185页

作者： Aparna raghavan Zahoor A. Shah Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences University of Toledo Department of pharmacology and Experimental Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo

Stroke management exerts insurmountable societal and economic burden on the patient as well as their caregivers. In the year 2010 alone, the direct and indirect costs of stroke care amounted to 36.5 billion dollars （Go et al., 2014）. Despite concentrated efforts to develop a safe, effective drug for stroke, we have not discovered one since the introduction of recombinant tissue plasminogen activator （rtpA）--the standalone FDA-approved therapy for stroke. While rtpA is highly effective, it needs to be given within 3-4.5 hours of the onset of stroke symptoms （Zivin, 2009）. This is often complicated by the delay in the commencement of treatment due to preliminary inclusion parameters that are required to be ascertained before rtpA administration.

关键词： Withania somnifera a pre-clinical study on neuroregenerative therapy for stroke MCAO pARp WS

Repair and regeneration properties of Ginkgo biloba after ischemic brain injury

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Neural Regeneration Research 2014年第11期9卷 1104-1107页

作者： Aparna raghavan Zahoor A.Shah Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences University of ToledoToledo OH USA

The irretrievable fate of neurons rhetoric for the first half of this dominated the neuroscience century, a position that was fiercely contested and recently debunked by extensive studies carried out in the field of neuroregeneration research. The turning point came in the year 1928, when Ramon Y. Cajal＇s （Lobato, 2008） work suggested that the regenerative capacity of neurons, though limited, could exist beyond their physical be- ing and depended on the environment surrounding them. That the manipulation of the restrictive environment surrounding the neuron could aid the regenerative process was conclusively established by Aguayo and colleagues （Richardson et al., 1980）. Since then, various strategies have been employed to target the different phases of regeneration which include： cell-replacement and augmenting endogenous neurogenesis, the use of trophic factors, reversal of the inhibitory cues, and induction of signal- ing pathways that stimulate axon growth and guidance （Horner and Gage. 2000）.

关键词： NSCs Repair and regeneration properties of Ginkgo biloba after ischemic brain injury EGb

Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and Notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)