{"title":"Ferroptosis: a potential therapeutic target for Alzheimer's disease.","authors":"Lan Yang, 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}
Paulina Śledzińska, Marek Bebyn, Jacek Furtak, Agnieszka Koper, Krzysztof Koper
{"title":"Current and promising treatment strategies in glioma.","authors":"Paulina Śledzińska, Marek Bebyn, Jacek Furtak, Agnieszka Koper, 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}
Christy M Richards, Seamus A McRae, Athena L Ranger, Andis Klegeris
{"title":"Extracellular histones as damage-associated molecular patterns in neuroinflammatory responses.","authors":"Christy M Richards, Seamus A McRae, Athena L Ranger, 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}
Roger D Traub, Miles A Whittington, Mark O Cunningham
{"title":"Simulation of oscillatory dynamics induced by an approximation of grid cell output.","authors":"Roger D Traub, Miles A Whittington, 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}
{"title":"Dietary inflammatory index and neuropsychiatric disorders.","authors":"Mahsa Golshani Nasab, Arash Heidari, Mohammadreza Sedighi, Narges Shakerian, Mona Mirbeyk, Amene Saghazadeh, Nima Rezaei","doi":"10.1515/revneuro-2023-0047","DOIUrl":"10.1515/revneuro-2023-0047","url":null,"abstract":"<p><p>Neuropsychiatric disorders (NPDs) are considered a potential threat to mental health. Inflammation predominantly plays a role in the pathophysiology of NPDs. Dietary patterns are widely postulated to be involved in the physiological response to inflammation. This review aims to discuss the literature on how dietary inflammatory index (DII) is related to inflammation and, consequently, NPDs. After comprehensive scrutiny in different databases, the articles that investigated the relation of DII score and various NPDs and psychological circumstances were included. The association between dietary patterns and mental disorders comprising depression, anxiety, and stress proved the role of a proinflammatory diet in these conditions' exacerbation. Aging is another condition closely associated with DII. The impact of proinflammatory and anti-inflammatory diet on sleep quality indicated related disorders like sleep latency and day dysfunctions among the different populations are in relation with the high DII score. The potential effects of genetic backgrounds, dietary patterns, and the gut microbiome on DII are discussed as well. To plan preventive or therapeutic interventions considering the DII, these factors, especially genetic variations, should be considered as there is a growing body of literature indicating the role of personalized medicine in different NPDs. To the best of our knowledge, there is a limited number of RCTs on this subject, so future research should evaluate the causality via RCTs and look for therapeutic interventions with an eye on personalized medicine using information about DII in NPDs.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"21-33"},"PeriodicalIF":3.4,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9830022","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":"Role of the basal ganglia in innate and learned behavioural sequences.","authors":"Natalia Favila, Kevin Gurney, Paul G Overton","doi":"10.1515/revneuro-2023-0038","DOIUrl":"10.1515/revneuro-2023-0038","url":null,"abstract":"<p><p>Integrating individual actions into coherent, organised behavioural units, a process called chunking, is a fundamental, evolutionarily conserved process that renders actions automatic. In vertebrates, evidence points to the basal ganglia - a complex network believed to be involved in action selection - as a key component of action sequence encoding, although the underlying mechanisms are only just beginning to be understood. Central pattern generators control many innate automatic behavioural sequences that form some of the most basic behaviours in an animal's repertoire, and in vertebrates, brainstem and spinal pattern generators are under the control of higher order structures such as the basal ganglia. Evidence suggests that the basal ganglia play a crucial role in the concatenation of simpler behaviours into more complex chunks, in the context of innate behavioural sequences such as chain grooming in rats, as well as sequences in which innate capabilities and learning interact such as birdsong, and sequences that are learned from scratch, such as lever press sequences in operant behaviour. It has been proposed that the role of the striatum, the largest input structure of the basal ganglia, might lie in selecting and allowing the relevant central pattern generators to gain access to the motor system in the correct order, while inhibiting other behaviours. As behaviours become more complex and flexible, the pattern generators seem to become more dependent on descending signals. Indeed, during learning, the striatum itself may adopt the functional characteristics of a higher order pattern generator, facilitated at the microcircuit level by striatal neuropeptides.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"35-55"},"PeriodicalIF":3.4,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9763772","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}
Lingyu Liu, Shen Sun, Wenjie Kang, Shuicai Wu, Lan Lin
{"title":"A review of neuroimaging-based data-driven approach for Alzheimer's disease heterogeneity analysis.","authors":"Lingyu Liu, Shen Sun, Wenjie Kang, Shuicai Wu, Lan Lin","doi":"10.1515/revneuro-2023-0033","DOIUrl":"10.1515/revneuro-2023-0033","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex form of dementia and due to its high phenotypic variability, its diagnosis and monitoring can be quite challenging. Biomarkers play a crucial role in AD diagnosis and monitoring, but interpreting these biomarkers can be problematic due to their spatial and temporal heterogeneity. Therefore, researchers are increasingly turning to imaging-based biomarkers that employ data-driven computational approaches to examine the heterogeneity of AD. In this comprehensive review article, we aim to provide health professionals with a comprehensive view of past applications of data-driven computational approaches in studying AD heterogeneity and planning future research directions. We first define and offer basic insights into different categories of heterogeneity analysis, including spatial heterogeneity, temporal heterogeneity, and spatial-temporal heterogeneity. Then, we scrutinize 22 articles relating to spatial heterogeneity, 14 articles relating to temporal heterogeneity, and five articles relating to spatial-temporal heterogeneity, highlighting the strengths and limitations of these strategies. Furthermore, we discuss the importance of understanding spatial heterogeneity in AD subtypes and their clinical manifestations, biomarkers for abnormal orderings and AD stages, the recent advancements in spatial-temporal heterogeneity analysis for AD, and the emerging role of omics data integration in advancing personalized diagnosis and treatment for AD patients. By emphasizing the significance of understanding AD heterogeneity, we hope to stimulate further research in this field to facilitate the development of personalized interventions for AD patients.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"121-139"},"PeriodicalIF":3.4,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134417","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}
Alexander Ya Rodnyy, Elena M Kondaurova, Anton S Tsybko, Nina K Popova, Dmitry A Kudlay, Vladimir S Naumenko
{"title":"The brain serotonin system in autism.","authors":"Alexander Ya Rodnyy, Elena M Kondaurova, Anton S Tsybko, Nina K Popova, Dmitry A Kudlay, Vladimir S Naumenko","doi":"10.1515/revneuro-2023-0055","DOIUrl":"10.1515/revneuro-2023-0055","url":null,"abstract":"<p><p>Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for <i>in vivo</i> regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT-related drugs have potential for ASD treatment.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"1-20"},"PeriodicalIF":3.4,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749517","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}
Andrea Corona-Trejo, María E Gonsebatt, Cristina Trejo-Solis, Victoria Campos-Peña, Laura Itzel Quintas-Granados, Edgar Yebrán Villegas-Vázquez, Octavio Daniel Reyes-Hernández, Vicente Jesús Hernández-Abad, Gabriela Figueroa-González, Daniela Silva-Adaya
{"title":"Transsulfuration pathway: a targeting neuromodulator in Parkinson's disease.","authors":"Andrea Corona-Trejo, María E Gonsebatt, Cristina Trejo-Solis, Victoria Campos-Peña, Laura Itzel Quintas-Granados, Edgar Yebrán Villegas-Vázquez, Octavio Daniel Reyes-Hernández, Vicente Jesús Hernández-Abad, Gabriela Figueroa-González, Daniela Silva-Adaya","doi":"10.1515/revneuro-2023-0039","DOIUrl":"10.1515/revneuro-2023-0039","url":null,"abstract":"<p><p>The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H<sub>2</sub>S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine β-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.</p>","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":" ","pages":"915-932"},"PeriodicalIF":4.1,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755171","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-frontmatter5","DOIUrl":"https://doi.org/10.1515/revneuro-2023-frontmatter5","url":null,"abstract":"","PeriodicalId":49623,"journal":{"name":"Reviews in the Neurosciences","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135409473","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}