Neurosignals最新文献

{"title":"A Comprehensive Review of Melatonin as Multi-Pathway Neuroprotectant Against Methamphetamine-Induced Programmed Cell Death: Discovery of the Circadian-Ferroptosis Axis.","authors":"Noel Pabalan, Sarawut Lapmanee, Phuntila Tharabenjasin, Panan Suntornsaratoon, Orapan Thosingha, Anorut Jenwitheesuk","doi":"10.33594/000000861","DOIUrl":"https://doi.org/10.33594/000000861","url":null,"abstract":"<p><strong>Introduction: </strong>Methamphetamine (METH) abuse affects 34 million individuals globally, causing severe neurotoxicity through multiple programmed cell death (PCD) pathways. No approved pharmacotherapies exist. We comprehensively examined melatonin's neuroprotective mechanisms against METH-induced apoptosis, pyroptosis, necroptosis, and ferroptosis.</p><p><strong>Methods: </strong>A comprehensive review of preclinical studies examining METH neurotoxicity mechanisms and melatonin's protective effects across all PCD pathways.</p><p><strong>Results: </strong>METH activates apoptosis, pyroptosis, necroptosis, and ferroptosis via distinct molecular pathways. Melatonin inhibits all pathways through antioxidant, mitochondrial, anti-inflammatory, and direct signaling effects. A circadian-ferroptosis axis was identified, linking circadian disruption to ferroptosis.</p><p><strong>Conclusions: </strong>Melatonin exhibits strong multi-target neuroprotection and represents a promising candidate for clinical translation.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"33 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Vitamin D Deficiency on Cognitive and Neuromuscular Functions in Elderly Patients.","authors":"Mohamed Ghalib Zakaria, Bassam Taha Saleh, Abdulsattar Hussein Abdullah","doi":"10.33594/000000836","DOIUrl":"https://doi.org/10.33594/000000836","url":null,"abstract":"<p><strong>Background/aims: </strong>Vitamin D plays an important regulatory role in neuronal and neuromuscular signalling, partly through its effects on calcium homeostasis, neuroinflammatory pathways, and vitamin D receptor-mediated transcription in neurons and glial cells. Deficiency of vitamin D is common among older adults and has been associated with impaired cognitive performance, reduced neuromuscular function, and elevated inflammatory activity. This study aimed to investigate associations between serum 25-hydroxyvitamin D levels, cognitive performance, neuromuscular function, and inflammatory signalling markers in older adults.</p><p><strong>Methods: </strong>A cross-sectional study was conducted over six months (March-August 2025) at Tikrit Teaching Hospital, enrolling 250 adults aged 65-85 years. Cognitive function was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment. Neuromuscular performance was evaluated by handgrip strength, gait speed, Timed Up and Go testing, bioelectrical impedance analysis, and electromyography. Serum 25-hydroxyvitamin D, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, creatine kinase, C-reactive protein, and interleukin-6 were measured. Associations were analyzed using Pearson correlations and group comparisons.</p><p><strong>Results: </strong>Vitamin D deficiency was prevalent in 62.0% of participants. Lower vitamin D levels were associated with reduced cognitive scores, weaker neuromuscular performance, altered calcium metabolism, and elevated inflammatory markers. Correlation analyses demonstrated moderate positive associations between vitamin D levels and cognitive and neuromuscular outcomes, and negative associations with inflammatory markers.</p><p><strong>Conclusion: </strong>Vitamin D deficiency in older adults is associated with impaired cognitive and neuromuscular function, potentially mediated by dysregulated calcium signalling and increased neuroinflammatory activity. These findings support a mechanistic link between vitamin D status and neuronal and neuromuscular communication pathways.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"32 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracing the Evolution and Recombination Events of Neurotropic Arenaviridae Viruses: a Bioinformatics Approach.","authors":"Meaad Hussein Al-Abadi, Bashar Talib Hameed Al-Nuaimi","doi":"10.33594/000000817","DOIUrl":"https://doi.org/10.33594/000000817","url":null,"abstract":"<p><p>Lassa virus is a member of the Arenaviridae family, a major cause of viral hemorrhagic fever. This virus is associated with severe neurological complications in a select group of patients. The evolutionary mechanisms behind genetic diversity, its adaptation, and its potential neuropathogenicity are still poorly understood. In this study, a comprehensive evolutionary analysis of the S and L genomes of Lassa virus was conducted, with an emphasis on ancestral reconstruction and genomic structure, as well as the identification of mutations that may contribute to viral adaptation leading to neurological disease. A set of complete S and L genomes was collected from NCBI. These sequences were carefully aligned using the MUSCLE algorithm to ensure a high match at each site. GTR+Gamma was used for evolutionary inference and was selected based on a statistical model test for its ability to accurately reflect the evolutionary dynamics of Lassa virus genomes. Phylogenetic trees were constructed using the maximum-likelihood algorithm RAxML, followed by careful preliminary analyses to assess the reliability of each branch in the tree. The mutations and recombination at the ancestral node were identified, which is likely a crucial point in the virus's ability to adapt and evolve. The emergence and distribution of major mutations across the viral lineage can be monitored. Notably, strains linked to known neurological problems frequently exhibit mutations, suggesting a possible link between certain genetic alterations and Lassa virus neuroinvasive characteristics. Our outcomes shed light on how genetic variety in the S and L segments impacts neurotropic virulence and offer important new insights into the evolutionary history and genomic adaptability of Lassa virus. In order to anticipate neurological risk, create targeted diagnostics, and direct the establishment of medical methods against neurotropic arenavirus infection, this study sets up the basis for future research.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"32 1","pages":"11-28"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Inflammation as a Biomarker of Disease Activity in Relapsing-Remitting MS.","authors":"Abdulsattar Hussein Abdullah","doi":"10.33594/000000814","DOIUrl":"10.33594/000000814","url":null,"abstract":"<p><strong>Background/aims: </strong>Relapsing-remitting multiple sclerosis (RRMS) is a chronic autoimmune disorder of the central nervous system, marked by unexpected episodes of neurological impairment and inflammation. Peripheral inflammatory indicators are becoming recognized as noninvasive predictors of disease activity, progression, and subsequent assessment, complementing traditional clinical and radiographic evaluations. To examine the correlations between disease activity and peripheral inflammatory biomarkers-interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and serum neurofilament light chain (sNfL)-in patients with relapsing-remitting multiple sclerosis (RRMS).</p><p><strong>Methods: </strong>Prospective observational research encompassed 250 RRMS patients from January 2024 to May 2025, who attended Tikrit Teaching Hospital and private neurology clinics. Patients received baseline and 12-month MRI scans, together with a clinical evaluation utilizing the Expanded Disability Status Scale (EDSS). Inflammatory markers and sNfL were assessed in peripheral blood samples. Investigations were conducted on the correlations among biomarkers, clinical impairment, and MRI lesion burden.</p><p><strong>Results: </strong>The average age of the population studied was 34.6 ± 8.7 years, and 64% of patients were women. Elevation of IL-6 (4.8 ± 2.0 pg/mL), TNF-α (6.1 ± 2.3 pg/mL), and hs-CRP and ESR sNfL (18.5 ± 6.4 pg/mL) with a positive correlation to EDSS score and MRI lesional load (p < 0.05) was observed. MRI showed a reduction in inflammatory lesions, whereas the number of black T1 holes increased over 12 months (indicating ongoing neurodegeneration).</p><p><strong>Conclusion: </strong>Soluble NfL, IL-6, and TNF-α are convenient markers of inflammation to reflect signal relay disease activity in RRMS. Their association with the clinical and radiographic findings may assist in personalizing the therapeutic approach.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"32 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant Hippocampal Neuroregenerative Plasticity in Schizophrenia: Reactive Neuroblastosis as a Possible Pathocellular Mechanism of Hallucination.","authors":"Mercy Priyadharshini Babu Deva Irakkam, Jerly Helan Mary Joseph, Mahesh Kandasamy","doi":"10.33594/000000712","DOIUrl":"https://doi.org/10.33594/000000712","url":null,"abstract":"<p><p>Hallucination is a sensory perception that occurs in the absence of external stimuli during abnormal neurological disturbances and various mental diseases. Hallucination is recognized as a core psychotic symptom and is particularly more prevalent in individuals with schizophrenia. Strikingly, a significant number of subjects with Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and other neurological diseases like cerebral stroke and epileptic seizure also experience hallucination. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the precise cellular mechanism accounting for hallucinations remains obscure. Neurogenesis is a cellular process of producing new neurons from the neural stem cells (NSC)-derived neuroblasts in the brain that contribute to the regulation of pattern separation, mood, olfaction, learning, and memory in adulthood. Impaired neurogenesis in the hippocampus of the adult brain has been linked to stress, anxiety, depression, and dementia. Notably, many neurodegenerative disorders are characterized by the mitotic and functional activation of neuroblasts and cell cycle re-entry of mature neurons leading to a drastic alteration in neurogenic process, known as reactive neuroblastosis. Considering their neurophysiological properties, the abnormal integration of neuroblasts into the existing neural network or withdrawal of their connections can lead to abnormal synaptogenesis, and neurotransmission. Eventually, this would be expected to result in altered perception accounting for hallucination. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes at the level of reactive neuroblastosis could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"31 1","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Narrative Review - Therapy Options and Therapy Failure in Retinoblastoma.","authors":"Argyrios Chronopoulos,&nbsp;Neele Babst,&nbsp;Christian Schiemenz,&nbsp;James S Schutz,&nbsp;Ludwig M Heindl,&nbsp;Mahdy Ranjbar,&nbsp;Vinodh Kakkassery","doi":"10.33594/000000585","DOIUrl":"https://doi.org/10.33594/000000585","url":null,"abstract":"<p><p>Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then preservation of the globe and useful vision. With modern treatment protocols and early disease detection success rates can reach up to 100% of disease-free-globe and eye preservation. Treatment of advanced cases remains complex, requiring aggressive chemotherapy or/and external beam radiation. Treatment protocols are extremely diverse and dependent on local resources thus success rates are variable. Here we review narratively current treatment protocols and failure rates based on a PubMed search using keywords of retinoblastoma, retinoblastoma seed, retinoblastoma treatment, enucleation.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"30 S1","pages":"39-58"},"PeriodicalIF":0.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.","authors":"Xiaojun Ju,&nbsp;Piotr Gaca,&nbsp;Wanlin Fan,&nbsp;Alexander C Rokohl,&nbsp;Yongwei Guo,&nbsp;Philomena A Wawer Matos,&nbsp;Steffen Emmert,&nbsp;Vinodh Kakkassery,&nbsp;Ludwig M Heindl","doi":"10.33594/000000560","DOIUrl":"https://doi.org/10.33594/000000560","url":null,"abstract":"<p><p>Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"30 S1","pages":"21-38"},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40636295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapy Resistance and Failure in Uveal Melanoma","authors":"","doi":"10.33594/000000555","DOIUrl":"https://doi.org/10.33594/000000555","url":null,"abstract":"Uveal Melanoma (UM), a common malignant intraocular tumor, is currently lacking a standard therapy. Traditional surgical approaches can result in patients losing organs or having difficult surgical procedures resulting in poor postoperative outcomes. Either way, there is no improvement in patients’ quality of life after surgery compared to radiotherapy. As a first-line treatment with radiotherapy, this therapy is limited by the size and location of the tumor. The risk of postoperative vision loss and second surgery for enucleation remains. UM is a special type of melanoma that is resistant to chemotherapy, and although the treatment is not effective, research has been investigated on this topic, suggesting new ideas for the treatment of UM - immunotherapy and targeted therapy. The current nivolumab plus ipilimumab treatment regimen has yielded relatively successful results, with some very encouraging case reports, but not as good as their efficacy in skin cancer. Despite the current unsatisfactory results of these new therapies, it is still the most attractive answer for UM that is highly metastatic and has a very poor prognosis. This review supports clinical decision-making and new treatment development by compiling the strengths and weaknesses of common treatments currently available in the clinic.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41439882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventional Radiotherapy (Brachytherapy) in Eyelid and Ocular Surface Tumors: A Review for Treatment of Naïve and Recurrent Malignancies.","authors":"Monica Maria Pagliara,&nbsp;Vinodh Kakkassery,&nbsp;Bruno Fionda,&nbsp;Domenico Lepore,&nbsp;György Kovács,&nbsp;Luca Tagliaferri,&nbsp;Maria Antonietta Blasi","doi":"10.33594/000000505","DOIUrl":"https://doi.org/10.33594/000000505","url":null,"abstract":"<p><p>The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"30 S1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40327785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increase of Kynurenic Acid after Encephalomyocarditis Virus Infection and Its Significances.","authors":"Halina Baran,&nbsp;Markus Draxler,&nbsp;Carina Kronsteiner,&nbsp;Berthold Kepplinger","doi":"10.33594/000000434","DOIUrl":"https://doi.org/10.33594/000000434","url":null,"abstract":"<p><strong>Background/aims: </strong>The moust symptoms of piglets infected with Encephalomyocarditis virus (EMCV) are related to breeding difficulty, circulation insufficiency, depression and occurrence of high lethality. An increase of tryptophan metabolism in the periphery and in the central nervous system (CNS) in human and non-human subjects with inflammatory diseases has been suggested. We investigated an alterations of tryptophan metabolite i.e. kynurenic acid (KYNA) level in the serum of piglets after EMC virus infection. In addition, we investigated the markers of immune stimulation i.e. neopterin and β2-microglobulin.</p><p><strong>Methods: </strong>KYNA was determined by high performance liquid chromatography method, while neopterin and β2-microglobulin by ELISA method. Piglets with an age of 8 weeks were infected intranasal and orally with the EMC virus. Blood samples were collected before virus inoculation at day 0 (control) and at 1, 2, 3 and 4 days post inoculation (DPI) and piglets as control subjects were used, too.</p><p><strong>Results: </strong>In EMCV infected piglets we observed a time dependent alteration of investigated parameters. KYNA level increased significantly and at 3 DPI was 341% of CO, p<0.001 and at 4 DPI an enhancement was 242% of CO, p<0.001, respectively. Neopterin increased moderately after EMCV infection and at 4 DPI was 130% of CO, p<0.05. Serum β2-microglobulin was slightly lowered and at 4 DPI was 86% of CO, p<0.05. Present data indicate an marked increase of kynurenine metabolism in the periphery after EMCV infection and an moderate activation of immune system.</p><p><strong>Conclusion: </strong>A marked increase of KYNA and a moderate enhancement of neopterin indicate sensibility of kynurenine metabolism to EMCV infection. Lowering of ß2-microgobulin might relate to development of events leading to the lethality. We suggest that due to viral infection an increase of KYNA might contribute to the inpairment of organs in the periphery and CNS function and might participate by sudden death.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"29 1","pages":"24-34"},"PeriodicalIF":0.0,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39472217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}