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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno Michael K.E.Schafer Sudena Wang Michael J.Schmeisser Axel Methner institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： Laura Huggon Emma L.Clayton UK Dementia Research institute at King’s College London LondonUK Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly *** and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

Asking one mechanism in glial cells during neuroinflammation

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Neural Regeneration Research 2025年第4期20卷 1077-1078页

作者： Xiaoli Guo Chikako Harada Takayuki Harada Visual Research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult *** autoimmune encephalomyelitis(EAE),an animal model of MS,is often used in preclinical *** data indicate that in addition to immune cells such as T cells and dendritic cells,CNS resident microglia and astrocytes play important roles in demyelinating neuroinflammation(Healy et al.,2022).In particular,microglia are key immune-competent cells that can respond to environmental *** depletion of transforming growth factor-β-activated kinase 1,a mitogen-associated protein kinase kinase kinase,in microglia is reported to reduce CNS inflammation and diminish axonal and myelin damage *** suggests that elucidating the mechanisms of microglia-specific responses during pathologies may help in the development of treatments that reduce EAE/MS disease severity(Goldmann et al.,2013).

关键词： inflammation clinical

Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

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Neural Regeneration Research 2025年第9期20卷 2579-2580页

作者： Thu Nguyen Minh Pham Christian Behl institute of Pathobiochemistry University Medical Center of the Johannes Gutenberg UniversityMainzGermany

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron *** entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to ***,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

关键词： cortex resistance Alzheimer

Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David J.Calkins Vanderbilt Eye institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge institute for medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

Monogenic gene therapy for glaucoma and optic nerve injury

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Neural Regeneration Research 2025年第3期20卷 815-816页

作者： Chikako Harada Xiaoli Guo Takayuki Harada Visual Research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells(RGCs) causes visual field defec... 详细信息

关键词： visual glaucoma degeneration

Crosstalk among canonical Wnt and Hippo pathway members in skeletal muscle and at the neuromuscular junction

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Neural Regeneration Research 2025年第9期20卷 2464-2479页

作者： Said Hashemolhosseini Lea Gessler institute of Biochemistry Medical FacultyFriedrich-Alexander-University of Erlangen-NürnbergErlangenGermany

Skeletal muscles are essential for locomotion,posture,and metabolic *** understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle *** process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle *** contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular *** muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate *** of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction *** development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as *** regulators coordinate the diffe rentiation of myoblasts into mature muscle *** pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient *** ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal *** interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular *** molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling *** recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular *** fact,research in the last few years now suggests that these two signaling pathways are interconnected and

关键词： canonical Wnt"Wingless-related integration site"pathway beta-catenin(CTNNB1) Hippo pathway myogenesis myotube neuromuscular junction satellite cell skeletal muscle fiber transcriptional co-activator with PDZ-binding motif(TAZ) T-cell-specific transcription factor/lymphoid enhancer-binding factor(TCF/LEF) TEA domain family member(TEAD) transducin-like enhancer of split(TLE) yes-associated protein 1(YAP1)

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li Department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing institute of Basic medical Sciences BeijingChina Hebei North University ZhangjiakouHebei ProvinceChina Beijing institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

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