Frontiers in Molecular Neuroscience最新文献

{"title":"Short- and long-term changes in neurological, behavioural, and blood biomarkers following repeated mild traumatic brain injury in rats-potential biological sex-dependent effects.","authors":"Rodrigo Moraga-Amaro, Oscar Moreno, Jordi Llop, Marion Bankstahl, Jens P Bankstahl","doi":"10.3389/fnmol.2025.1488261","DOIUrl":"10.3389/fnmol.2025.1488261","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease resulting from repeated mild traumatic brain injuries (rmTBI). The necessity for diagnosis of CTE, which can so far only be confirmed after post-mortem, is a pressing need. New approaches to early diagnose this disease are crucial to facilitate the translation of novel treatment strategies to the clinic. Several studies have found suitable candidate biomarkers, but the results are not straightforward. As biological sex is suggested to be a major confounding factor, we explored how sex influences behavioural and candidate blood biomarkers during CTE-like progression following experimental rmTBI.</p><p><strong>Methods: </strong>To induce CTE-like development, we subjected male and female rats to three mTBIs at a 5-day interval. We then monitored and analysed differences in neurological, behavioural, and physiological parameters up to 12 weeks after the injuries-both by sex and grouped-and underwent further analysis using generalised estimated equation (GEE). To determine long-term changes in tau aggregation as a hallmark of CTE, we used [¹⁸F]-florzolotau (florzolotau) autoradiography in brain slices.</p><p><strong>Results: </strong>Both short-term weight gain and time-to-right after rmTBI were increased in grouped animals, with male rats showing more prominent changes. The neurological state was impaired after each mTBI and still 12 weeks later, independent of the sex. A protracted anhedonic-like behaviour due to rmTBI was found at the group level only at week 2 but remained continuously present in male rats. While spatial memory was not impaired, male rats showed increased anxiety-like behaviour. Moreover, neuron-specific enolase (NSE) was elevated in the blood 1 day after rmTBI, but only in females. On the contrary, blood p-tau was increased 3 days after rmTBI only in males. In addition, male rats showed significantly increased florzolotau binding in the brain after 12 weeks, suggesting brain contusion causes increased tau aggregation. Interestingly, brain neurofibrillary tangles (NFTs) at 12 weeks after rmTBI showed a strong correlation with the neurological state at 1 day after rmTBI.</p><p><strong>Discussion: </strong>Taken together, our findings suggest that male rats may be more susceptible to short-and long-term consequences of rmTBI in the applied model. These sex differences should be considered when translating preclinical biomarker candidates to the clinic. Understanding these differences could guide the diagnosis and treatment of CTE in a personalized manner, offering hope for more effective treatments in the future.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1488261"},"PeriodicalIF":3.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11814444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407095","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":"Regulatory mechanism of Reelin activity: a platform for exploiting Reelin as a therapeutic agent.","authors":"Mitsuharu Hattori","doi":"10.3389/fnmol.2025.1546083","DOIUrl":"10.3389/fnmol.2025.1546083","url":null,"abstract":"<p><p>Reelin is a secreted glycoprotein that was initially investigated in the field of neuronal development. However, in recent decades, its role in the adult brain has become increasingly important, and it is now clear that diminished Reelin function is involved in the pathogenesis and progression of neuropsychiatric and neurodegenerative disorders, including schizophrenia and Alzheimer's disease (AD). Reelin activity is regulated at multiple steps, including synthesis, posttranslational modification, secretion, oligomerization, proteolytic processing, and interactions with extracellular molecules. Moreover, the differential use of two canonical receptors and the presence of non-canonical receptors and co-receptors add to the functional diversity of Reelin. In this review, I summarize recent findings on the molecular mechanisms of Reelin activity. I also discuss possible strategies to enhance Reelin's function. A complete understanding of Reelin function and its regulatory mechanisms in the adult central nervous system could help ameliorate neuropsychiatric and neurodegenerative disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1546083"},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390590","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":"Brain network and energy imbalance in Parkinson's disease: linking ATP reduction and <i>α</i>-synuclein pathology.","authors":"Hirohisa Watanabe, Sayuri Shima, Kazuya Kawabata, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito","doi":"10.3389/fnmol.2024.1507033","DOIUrl":"10.3389/fnmol.2024.1507033","url":null,"abstract":"<p><p>Parkinson's disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in the pentose phosphate pathway and purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple brain functions, require significant energy due to their dense synaptic activity and long-range connections. Deficits in ATP production in PD can severely impair these hubs. The energy imbalance also affects subcortical regions, including the massive axonal arbors in the striatum of substantia nigra pars compacta neurons, due to their high metabolic demand. This ATP decline may result in <i>α</i>-synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown and accelerated neurodegeneration. We propose an \"ATP Supply-Demand Mismatch Model\" to help explain the pathogenesis of PD. This model emphasizes how ATP deficits drive pathological protein aggregation, impaired autophagy, and the degeneration of key brain networks, contributing to both motor and non-motor symptoms.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1507033"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254346","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":"A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response.","authors":"Allie Lipshutz, Victoria Saltz, Kristin R Anderson, Alessia Manganaro, Dani Dumitriu","doi":"10.3389/fnmol.2025.1347539","DOIUrl":"10.3389/fnmol.2025.1347539","url":null,"abstract":"<p><strong>Introduction: </strong>The neurobiological basis for individual variability in behavioral responses to stimuli remains poorly understood. Probing the neural substrates that underlie individual variability in stress responses may open the door for preventive approaches that use biological markers to identify at-risk populations. New developments of viral neuronal tracing tools have led to a recent increase in studies on long range circuits and their functional role in stress responses and social behavior. While these studies are necessary to untangle largescale connectivity, most social behaviors are mediated and fine-tuned by local subregional circuitry.</p><p><strong>Methods: </strong>In order to probe this local, interregional connectivity, we present a new combination of a neuronal tracing system with immediate early gene immunohistochemistry for examining structural and functional connectivity within the same animal. Specifically, we combine a retrograde transsynaptic rabies tracing system with cFos colocalization immediately after an acute stressor to elucidate local structural and stress-activated connectivity within the amygdala complex in female and male mice.</p><p><strong>Results and discussion: </strong>We show how specific structural and functional connections can predict individual variability along a spectrum of social approach/avoidance following acute social defeat stress. We demonstrate how our robust method can be used to elucidate structural and functional differences in local connectivity that mediate individual variability in behavioral response.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1347539"},"PeriodicalIF":3.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364401","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":"Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward.","authors":"Michael Fritz, Priscila Batista Rosa, Daniel Wilhelms, Maarit Jaarola, Johan Ruud, David Engblom, Anna M Klawonn","doi":"10.3389/fnmol.2024.1418686","DOIUrl":"10.3389/fnmol.2024.1418686","url":null,"abstract":"<p><p>The neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of α7 nAChRs in mice attenuates cocaine seeking in a Pavlovian conditioned place preference paradigm and decreases operant responding to cocaine in a runway task and in self-administration, without influencing responding to palatable food. This effect can be attributed to alpha 7 receptor signaling in the striatum, as selective deletion of striatal α7 nAChRs using a viral vector approach resulted in a similar decrease in cocaine-preference as that of global deletion. To investigate which type of striatal neurons are responsible for this effect, we selectively targeted Cholinergic (ChAT-expressing) neurons and dopamine D1-receptor (D1R) expressing neurons. Mice with conditional deletion of α7 nAChRs in ChAT-neurons (α7 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while α7 nAChR-D1RCre mice had no changes in reward learning to neither food nor cocaine. Cocaine induction of striatal immediate early gene expression of cFos, FosB, Arc and EGR2 was blocked in α7 nAChR-ChATCre mice, demonstrating the importance of α7 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that α7 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1418686"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188927","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":"Impact of modulating leptin sensitivity on the transcriptomic profile of adult-derived hypothalamic mouse neurons.","authors":"Ewa Ocłoń, Artur Gurgul, Tomasz Szmatoła, Igor Jasielczuk, Miroslaw Kucharski, Joanna Zubel-Łojek, Dorota Anna Zieba","doi":"10.3389/fnmol.2024.1518737","DOIUrl":"10.3389/fnmol.2024.1518737","url":null,"abstract":"<p><p>The modulation of leptin sensitivity in hypothalamic neurons plays a crucial role in metabolic regulation and the development of obesity. Three distinct approaches, exposure to leptin (LEPA), administration of leptin antagonist (LANTA), and treatment with palmitate (PA), were explored in this study to assess their effects on adult-derived mHypoA-2/12 neurons and the resulting transcriptomic signatures. To this end, 3' mRNA-Seq transcriptome analysis was employed, unexpectedly revealing downregulation of key genes associated with the NOD-like receptor signaling pathway (<i>Irf9</i>, <i>Mapk3</i>, <i>Stat2</i>, <i>Nfkbia</i>, <i>Ikbkg</i>, <i>Rela</i>, <i>Cxcl1</i>, and <i>Traf5</i>), the C-type lectin receptor signaling pathway (<i>Nfkb2</i>, <i>Irf9</i>, <i>Mapk3</i>, <i>Stat2</i>, <i>Nfkbia</i>, <i>Ikbkg</i>, <i>Rela</i>, and <i>Ptgs2</i>), the NF kappa B signaling pathway (<i>Nfkbia</i>, <i>Ikbkg</i>, <i>Nfkb2</i>, <i>Rela</i>, <i>Traf5</i>, <i>Cxcl1</i>, and <i>Ptgs2</i>), and the IL 17 signaling pathway (<i>Nfkbia</i>, <i>Ikbkg</i>, <i>Mapk3</i>, <i>Rela</i>, <i>Traf5</i>, <i>Cxcl1</i>, and <i>Ptgs2</i>). These findings help elucidate the molecular mechanisms through which these factors influence leptin sensitivity and provide insights into the pathways implicated in the development of leptin resistance in hypothalamic neurons. The surprising downregulation of these pathways suggests a complex interplay between leptin signaling and the cellular stress response in hypothalamic neurons. This alteration may reflect adaptive mechanisms in response to prolonged leptin or fatty acid exposure. Understanding these dynamics is essential for elucidating the role of hypothalamic inflammation in the progression of leptin resistance and associated metabolic disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1518737"},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364385","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":"Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.","authors":"Pavel Uvarov, Satoshi Fudo, Cem Karakus, Andrey Golubtsov, Federico Rotondo, Tatiana Sukhanova, Shetal Soni, Coralie Di Scala, Tommi Kajander, Claudio Rivera, Anastasia Ludwig","doi":"10.3389/fnmol.2024.1505722","DOIUrl":"10.3389/fnmol.2024.1505722","url":null,"abstract":"<p><strong>Introduction: </strong>The neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.</p><p><strong>Methods: </strong>To identify novel CTD regulatory motifs, we used the Mu transposon-based mutagenesis system to generate a library of KCC2 mutants with 5 amino acid insertions randomly distributed within the KCC2-CTD. We determined the insertion positions in 288 mutants by restriction analysis and selected clones with a single insertion site outside known KCC2 regulatory motifs. We analyzed the subcellular distribution of KCC2-CTD mutants in cultured cortical neurons using immunocytochemistry and selected ten mutants with ectopic expression patterns for detailed characterization.</p><p><strong>Results: </strong>A fluorescent Cl^--transport assay in HEK293 cells revealed mutants with both reduced and enhanced Cl^--extrusion activity, which overall correlated with their glycosylation patterns. Live-cell immunostaining analysis of plasma membrane expression of KCC2-CTD mutants in cultured cortical neurons corroborated the glycosylation data. Furthermore, the somatodendritic chloride gradient in neurons transfected with the KCC2-CTD mutants correlated with their Cl^--extrusion activity in HEK293 cells. Gain- and loss-of-function mutant positions were analyzed using available KCC2 cryo-EM structures.</p><p><strong>Discussion: </strong>Two groups of mutants were identified based on 3D structural analysis. The first group, located near the interface of transmembrane and cytoplasmic domains, may affect interactions with the N-terminal inhibitory peptide regulating KCC2 activity. The second group, situated on the external surface of the cytoplasmic domain, may disrupt interactions with regulatory proteins. Analyzing CTD mutations that modulate KCC2 activity enhances our understanding of its function and is essential for developing novel anti-seizure therapies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1505722"},"PeriodicalIF":3.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065119","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":"Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.","authors":"Yinyin Xie, Wenlin Sun, Aoya Han, Xinru Zhou, Shijie Zhang, Changchang Shen, Yi Xie, Cui Wang, Nanchang Xie","doi":"10.3389/fnmol.2024.1527013","DOIUrl":"10.3389/fnmol.2024.1527013","url":null,"abstract":"<p><p>Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson's disease, Charcot-Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1527013"},"PeriodicalIF":3.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058774","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":"Editorial: Oxytosis/ferroptosis: unraveling the mechanisms and its multifaceted role in neurodegenerative diseases.","authors":"Nawab John Dar, David Soriano Castell, Shahnawaz Ali Bhat, Pamela Maher","doi":"10.3389/fnmol.2024.1547301","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1547301","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1547301"},"PeriodicalIF":3.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052324","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":"The current state of knowledge on the role of NKG2D ligands in multiple sclerosis and other autoimmune diseases.","authors":"Aleksandra Pogoda-Wesołowska, Nina Sługocka, Agnieszka Synowiec, Klaudia Brodaczewska, Marcin Mejer-Zahorowski, Maciej Ziękiewicz, Wojciech Szypowski, Piotr Szymański, Adam Stępień","doi":"10.3389/fnmol.2024.1493308","DOIUrl":"10.3389/fnmol.2024.1493308","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with demyelinating inflammatory characteristics. It is the most common nontraumatic and disabling disease affecting young adults. The incidence and prevalence of MS have been increasing. However, its exact cause remains unclear. The main tests used to support the diagnosis are magnetic resonance imaging (MRI) examination and cerebrospinal fluid (CSF) analysis. Nonetheless, to date, no sensitive or specific marker has been identified for the detection of the disease at its initial stage. In recent years, researchers have focused on the fact that the number of natural killer cell group 2 member D (NKG2D) family of C-type lectin-like receptor + (NKG2D+) T cells in the peripheral blood, CSF, and brain tissue has been shown to be higher in patients with MS than in controls. The activating receptor belonging to the NKG2D is stimulated by specific ligands: in humans these are major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) proteins and UL16 binding 1-6 proteins (ULBP1-6). Under physiological conditions, the aforementioned ligands are expressed at low or undetectable levels but can be induced in response to stress factors. NKG2D ligands (NKG2DLs) are involved in epigenetic regulation of their expression. To date, studies in cell cultures, animal models, and brain tissues have revealed elevated expression of MICA/B, ULPB4, and its mouse homolog murine UL16 binding protein-like transcript (MULT1), in oligodendrocytes and astrocytes from patients with MS. Furthermore, soluble forms of NKG2DLs were elevated in the plasma and CSF of patients with MS compared to controls. In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1493308"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046374","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}