Reviews in the Neurosciences最新文献

{"title":"Targeting NMDA receptor signaling for therapeutic intervention in brain disorders.","authors":"He Chen,&nbsp;Yuanping Dong,&nbsp;Yun Wu,&nbsp;Feng Yi","doi":"10.1515/revneuro-2022-0096","DOIUrl":"https://doi.org/10.1515/revneuro-2022-0096","url":null,"abstract":"<p><p><i>N</i>-Methyl-d-aspartate (NMDA) receptor hyperfunction plays a key role in the pathological processes of depression and neurodegenerative diseases, whereas NMDA receptor hypofunction is implicated in schizophrenia. Considerable efforts have been made to target NMDA receptor function for the therapeutic intervention in those brain disorders. In this mini-review, we first discuss ion flux-dependent NMDA receptor signaling and ion flux-independent NMDA receptor signaling that result from structural rearrangement upon binding of endogenous agonists. Then, we review current strategies for exploring druggable targets of the NMDA receptor signaling and promising future directions, which are poised to result in new therapeutic agents for several brain disorders.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"34 6","pages":"635-647"},"PeriodicalIF":4.1,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning the circadian system with light treatment for Parkinson's disease: an in-depth, critical review.","authors":"Gregory L Willis, Stuart M Armstrong","doi":"10.1515/revneuro-2023-0026","DOIUrl":"10.1515/revneuro-2023-0026","url":null,"abstract":"<p><p>Late in the twentieth century, interest intensified regarding the involvement of the circadian system in the aetiology and treatment of Parkinson's disease (PD). It has been envisaged that this approach might provide relief beyond the limited benefits and severe side effects achieved by dopamine (DA) replacement. In the first clinical article, published in 1996, polychromatic light was used to shift the circadian clock as it is considered to be the most powerful zeitgeber (time keeper) that can be implemented to realign circadian phase. Since that time, 11 additional articles have implemented light treatment (LT) in various forms as an adjuvant to DA replacement. In spite of the growing interest in this area, the systematic exploration of LT in PD has been stymied by several methodological factors. Such factors include time of LT presentation, duration of studies undertaken, frequency of light employed, dose of light prescribed and relevance of experimental design to the prolonged course of the illness. On this basis, it is the purpose of this review to provide an in-depth examination of these papers, and the underlying preclinical work, to provide critique, thereby giving direction for future studies in therapeutic applications of LT for PD. Consideration of this collective work may serve to carve a path for future research and thereby improve the lives of those suffering from this debilitating disorder.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"57-84"},"PeriodicalIF":3.4,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral inflammation is a potential etiological factor in Alzheimer's disease.","authors":"Ziyuan Li, Hui Wang, Yafu Yin","doi":"10.1515/revneuro-2023-0049","DOIUrl":"10.1515/revneuro-2023-0049","url":null,"abstract":"<p><p>Peripheral inflammation could constitute a risk factor for AD. This review summarizes the research related to peripheral inflammation that appears to have a relationship with Alzheimer's disease. We find there are significant associations between AD and peripheral infection induced by various pathogens, including herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, <i>Porphyromonas gingivalis</i>, <i>Helicobacter pylori</i>, and <i>Toxoplasma gondii</i>. Chronic inflammatory diseases are also reported to contribute to the pathophysiology of AD. The mechanisms by which peripheral inflammation affects the pathophysiology of AD are complex. Pathogen-derived neurotoxic molecule composition, disrupted BBB, and dysfunctional neurogenesis may all play a role in peripheral inflammation, promoting the development of AD. Anti-pathogenic medications and anti-inflammatory treatments are reported to decrease the risk of AD. Studies that could improve understanding the associations between AD and peripheral inflammation are needed. If our assumption is correct, early intervention against inflammation may be a potential method of preventing and treating AD.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"99-120"},"PeriodicalIF":3.4,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis underlying hexanucleotide repeat expansions in <i>C9orf72</i> gene in amyotrophic lateral sclerosis.","authors":"Zhao Zhong Chong, Daniel L Menkes, Nizar Souayah","doi":"10.1515/revneuro-2023-0060","DOIUrl":"10.1515/revneuro-2023-0060","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Mutations in <i>C9orf72</i> and the resulting hexanucleotide repeat (GGGGCC) expansion (HRE) has been identified as a major cause of familial ALS, accounting for about 40 % of familial and 6 % of sporadic cases of ALS in Western patients. The pathological outcomes of HRE expansion in ALS have been recognized as the results of two mechanisms that include both the toxic gain-of-function and loss-of-function of C9ORF72. The gain of toxicity results from RNA and dipeptide repeats (DPRs). The HRE can be bidirectionally transcribed into RNA foci, which can bind to and disrupt RNA splicing, transport, and translation. The DPRs that include poly-glycine-alanine, poly-glycine-proline, poly-glycine- arginine, poly-proline-alanine, and poly-proline-arginine can induce toxicity by direct binding and sequestrating other proteins to interfere rRNA synthesis, ribosome biogenesis, translation, and nucleocytoplasmic transport. The C9ORF72 functions through binding to its partners-Smith-Magenis chromosome regions 8 (SMCR8) and WD repeat-containing protein (WDR41). Loss of C9ORF72 function results in impairment of autophagy, deregulation of autoimmunity, increased stress, and disruption of nucleocytoplasmic transport. Further insight into the mechanism in C9ORF72 HRE pathogenesis will facilitate identifying novel and effective therapeutic targets for ALS.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"85-97"},"PeriodicalIF":3.4,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9911300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontmatter","authors":"","doi":"10.1515/revneuro-2023-frontmatter6","DOIUrl":"https://doi.org/10.1515/revneuro-2023-frontmatter6","url":null,"abstract":"","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136065437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of microglia in chronic neuropathic pain associated with spinal cord injury - a systematic review.","authors":"David Ramos, Célia Duarte Cruz","doi":"10.1515/revneuro-2023-0031","DOIUrl":"10.1515/revneuro-2023-0031","url":null,"abstract":"<p><p>In recent decade microglia have been found to have a central role in the development of chronic neuropathic pain after injury to the peripheral nervous system. It is widely accepted that peripheral nerve injury triggers microglial activation in the spinal cord, which contributes to heightened pain sensation and eventually chronic pain states. The contribution of microglia to chronic pain arising after injury to the central nervous system, such as spinal cord injury (SCI), has been less studied, but there is evidence supporting microglial contribution to central neuropathic pain. In this systematic review, we focused on post-SCI microglial activation and how it is linked to emergence and maintenance of chronic neuropathic pain arising after SCI. We found that the number of studies using animal SCI models addressing microglial activity is still small, compared with the ones using peripheral nerve injury models. We have collected 20 studies for full inclusion in this review. Many mechanisms and cellular interactions are yet to be fully understood, although several studies report an increase of density and activity of microglia in the spinal cord, both in the vicinity of the injury and in the spared spinal tissue, as well as in the brain. Changes in microglial activity come with several molecular changes, including expression of receptors and activation of signalling pathways. As with peripheral neuropathic pain, microglia seem to be important players and might become a therapeutic target in the future.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"933-950"},"PeriodicalIF":4.1,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9920089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis: a potential therapeutic target for Alzheimer's disease.","authors":"Lan Yang,&nbsp;Jianfei Nao","doi":"10.1515/revneuro-2022-0121","DOIUrl":"https://doi.org/10.1515/revneuro-2022-0121","url":null,"abstract":"<p><p>The most prevalent dementia-causing neurodegenerative condition is Alzheimer's disease (AD). The aberrant buildup of amyloid β and tau hyperphosphorylation are the two most well-known theories about the mechanisms underlying AD development. However, a significant number of pharmacological clinical studies conducted around the world based on the two aforementioned theories have not shown promising outcomes, and AD is still not effectively treated. Ferroptosis, a non-apoptotic programmed cell death defined by the buildup of deadly amounts of iron-dependent lipid peroxides, has received more attention in recent years. A wealth of data is emerging to support the role of iron in the pathophysiology of AD. Cell line and animal studies applying ferroptosis modulators to the treatment of AD have shown encouraging results. Based on these studies, we describe in this review the underlying mechanisms of ferroptosis; the role that ferroptosis plays in AD pathology; and summarise some of the research advances in the treatment of AD with ferroptosis modulators. We hope to contribute to the clinical management of AD.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"34 5","pages":"573-598"},"PeriodicalIF":4.1,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and promising treatment strategies in glioma.","authors":"Paulina Śledzińska,&nbsp;Marek Bebyn,&nbsp;Jacek Furtak,&nbsp;Agnieszka Koper,&nbsp;Krzysztof Koper","doi":"10.1515/revneuro-2022-0060","DOIUrl":"https://doi.org/10.1515/revneuro-2022-0060","url":null,"abstract":"<p><p>Gliomas are the most common primary central nervous system tumors; despite recent advances in diagnosis and treatment, glioma patients generally have a poor prognosis. Hence there is a clear need for improved therapeutic options. In recent years, significant effort has been made to investigate immunotherapy and precision oncology approaches. The review covers well-established strategies such as surgery, temozolomide, PCV, and mTOR inhibitors. Furthermore, it summarizes promising therapies: tumor treating fields, immune therapies, tyrosine kinases inhibitors, IDH(Isocitrate dehydrogenase)-targeted approaches, and others. While there are many promising treatment strategies, none fundamentally changed the management of glioma patients. However, we are still awaiting the outcome of ongoing trials, which have the potential to revolutionize the treatment of glioma.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"34 5","pages":"483-516"},"PeriodicalIF":4.1,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular histones as damage-associated molecular patterns in neuroinflammatory responses.","authors":"Christy M Richards,&nbsp;Seamus A McRae,&nbsp;Athena L Ranger,&nbsp;Andis Klegeris","doi":"10.1515/revneuro-2022-0091","DOIUrl":"https://doi.org/10.1515/revneuro-2022-0091","url":null,"abstract":"<p><p>The four core histones H2A, H2B, H3, H4, and the linker histone H1 primarily bind DNA and regulate gene expression within the nucleus. Evidence collected mainly from the peripheral tissues illustrates that histones can be released into the extracellular space by activated or damaged cells. In this article, we first summarize the innate immune-modulatory properties of extracellular histones and histone-containing complexes, such as nucleosomes, and neutrophil extracellular traps (NETs), described in peripheral tissues. There, histones act as damage-associated molecular patterns (DAMPs), which are a class of endogenous molecules that trigger immune responses by interacting directly with the cellular membranes and activating pattern recognition receptors (PRRs), such as toll-like receptors (TLR) 2, 4, 9 and the receptor for advanced glycation end-products (RAGE). We then focus on the available evidence implicating extracellular histones as DAMPs of the central nervous system (CNS). It is becoming evident that histones are present in the brain parenchyma after crossing the blood-brain barrier (BBB) or being released by several types of brain cells, including neurons, microglia, and astrocytes. However, studies on the DAMP-like effects of histones on CNS cells are limited. For example, TLR4 is the only known molecular target of CNS extracellular histones and their interactions with other PRRs expressed by brain cells have not been observed. Nevertheless, extracellular histones are implicated in the pathogenesis of a variety of neurological disorders characterized by sterile neuroinflammation; therefore, detailed studies on the role these proteins and their complexes play in these pathologies could identify novel therapeutic targets.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"34 5","pages":"533-558"},"PeriodicalIF":4.1,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9783226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation of oscillatory dynamics induced by an approximation of grid cell output.","authors":"Roger D Traub,&nbsp;Miles A Whittington,&nbsp;Mark O Cunningham","doi":"10.1515/revneuro-2022-0107","DOIUrl":"https://doi.org/10.1515/revneuro-2022-0107","url":null,"abstract":"<p><p>Grid cells, in entorhinal cortex (EC) and related structures, signal animal location relative to hexagonal tilings of 2D space. A number of modeling papers have addressed the question of how grid firing behaviors emerge using (for example) ideas borrowed from dynamical systems (attractors) or from coupled oscillator theory. Here we use a different approach: instead of asking how grid behavior emerges, we take as a given the experimentally observed intracellular potentials of superficial medial EC neurons during grid firing. Employing a detailed neural circuit model modified from a lateral EC model, we then ask how the circuit responds when group of medial EC principal neurons exhibit such potentials, simultaneously with a simulated theta frequency input from the septal nuclei. The model predicts the emergence of robust theta-modulated gamma/beta oscillations, suggestive of oscillations observed in an <i>in vitro</i> medial EC experimental model (Cunningham, M.O., Pervouchine, D.D., Racca, C., Kopell, N.J., Davies, C.H., Jones, R.S.G., Traub, R.D., and Whittington, M.A. (2006). Neuronal metabolism governs cortical network response state. Proc. Natl. Acad. Sci. U S A 103: 5597-5601). Such oscillations result because feedback interneurons tightly synchronize with each other - despite the varying phases of the grid cells - and generate a robust inhibition-based rhythm. The lack of spatial specificity of the model interneurons is consistent with the lack of spatial periodicity in parvalbumin interneurons observed by Buetfering, C., Allen, K., and Monyer, H. (2014). Parvalbumin interneurons provide grid cell-driven recurrent inhibition in the medial entorhinal cortex. Nat. Neurosci. 17: 710-718. If <i>in vivo</i> EC gamma rhythms arise during exploration as our model predicts, there could be implications for interpreting disrupted spatial behavior and gamma oscillations in animal models of Alzheimer's disease and schizophrenia. Noting that experimental intracellular grid cell potentials closely resemble cortical Up states and Down states, during which fast oscillations also occur during Up states, we propose that the co-occurrence of slow principal cell depolarizations and fast network oscillations is a general property of the telencephalon, in both waking and sleep states.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"34 5","pages":"517-532"},"PeriodicalIF":4.1,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329426/pdf/revneuro-34-5-revneuro-2022-0107.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}