CNS & neurological disorders drug targets最新文献

{"title":"Myelin and Oligodendrocyte Dysfunction in Demyelinating and Neurodegenerative Disorders: Signaling Pathways and Therapeutic Targets.","authors":"Shivang Shukla, Vivek Srivastava, Harshita Gaur, Anjali Rai","doi":"10.2174/0118715273437393260729093129","DOIUrl":"https://doi.org/10.2174/0118715273437393260729093129","url":null,"abstract":"<p><strong>Introduction: </strong>Oligodendrocytes (OLs) synthesize myelin, a substance that plays a significant role in ensuring proper functioning of the Central Nervous System (CNS). Myelin abnormalities are involved in disease pathogenesis in AD, MS, and ALS. In contrast, MS involves autoimmune reactions directed against myelin. On the other hand, AD and ALS are characterized by neurodegeneration. This article seeks to give a critical discussion on myelin and OL dysfunction in these diseases, among others.</p><p><strong>Methods: </strong>A narrative literature search was carried out in various databases including Scopus, Google Scholar, Web of Science, and PubMed, focusing on papers relating to myelination, remyelination, and OLs, particularly those addressing signaling pathways and treatment strategies.</p><p><strong>Results: </strong>MS is an autoimmune disease characterized by inflammation that causes demyelination and OL dysfunction. Oxidative stress and mitochondrial dysfunction play roles in the pathogenesis of ALS, whereas AD is a result of disrupted neuronal supportive functions and myelin damage. Important signaling pathways involved in OL formation and myelin repair include the Wnt/β-catenin, AKT/mTOR, and ERK/MAPK pathways. Drugs like edaravone, ocrelizumab, and siponimod have been identified for promoting myelin repair.</p><p><strong>Discussion: </strong>The relationship between abnormal oligodendrocyte function, demyelination, and specific disease-related pathological processes demonstrates that although there is a similarity among MS, AD, and ALS, each condition possesses its own unique molecular foundation. One potential treatment approach would be targeting shared signaling pathways relevant to myelination and remyelination. Nonetheless, disease variability and specific pathogenic characteristics demand a targeted therapy approach.</p><p><strong>Conclusion: </strong>Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases. Targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803068","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":"From Molecules to Minds: Redefining the Power of Psychedelics and Entactogens in Treating Brain Disorders.","authors":"Sampriti Paul, Sonal Dubey, Mayur Yergeri Chandrasekharappa, Prashant Tiwari","doi":"10.2174/0118715273452468260729080541","DOIUrl":"https://doi.org/10.2174/0118715273452468260729080541","url":null,"abstract":"<p><p>Recent advances in neuropsychopharmacology have renewed interest in psychedelics and entactogens as potential treatments for brain disorders, owing to their rapid effects on neural plasticity, cognition, and affect. Classical serotonergic psychedelics primarily act as 5-HT2A receptor agonists with additional activity at 5-HT1A and other serotonin receptors, whereas entactogens such as MDMA enhance monoamine release through transporter interactions. These actions converge on glutamatergic circuits, intracellular signaling cascades and transcriptional programs that can remodel synaptic connectivity. At the cellular level, psychedelics and entactogens acutely induce immediate early genes, including c-Fos, EGR1 and NPAS4, which regulate downstream targets such as BDNF and Arc to promote neuritogenesis, dendritic spinogenesis and synaptogenesis in cortical and hippocampal networks. Complementary epigenetic changes in DNA methylation and histone acetylation may help sustain these transcriptional effects beyond the period of drug exposure. In parallel, these compounds modulate neuroimmune pathways via 5-HT2A and sigma-1-receptors, altering cytokine profiles and microglial activation in a context-dependent manner rather than exerting a uniform antiinflammatory class effect. Preclinical studies and early clinical trials suggest that psychedelics and entactogens can produce rapid and sometimes durable improvements in mood and anxiety symptoms and are being investigated for conditions such as major depressive disorder, post-traumatic stress disorder, obsessive-compulsive disorder, substance use disorder and selected neurodegenerative syndromes. However, most indications remain supported only by small or early-phase studies and evidence for disease modification, particularly in Alzheimer's disease-related dementia, is currently limited to mechanistic hypotheses and preclinical models. This review synthesizes current knowledge on the receptor-level, molecular, genetic and immunological mechanisms of psychedelics and entactogens, linking these processes to neuroplasticity and brain network reorganization. It also discusses emerging therapeutic evidence, safety considerations and evolving regulatory frameworks, highlighting critical knowledge gaps and priorities for future research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803086","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":"An Innovative Strategy for Treating Neurodegenerative Disorders through Exosome-based Smart Delivery Systems: A Comprehensive Review.","authors":"M D Abubakar, Ritu Dahiya, Lokesh Nama, Kanika Goyal, Abhishek Ambawatiya, Mamta Bishnoi, Amita Rai, Krishna Murti, Nitesh Kumar","doi":"10.2174/0118715273453626260724060812","DOIUrl":"https://doi.org/10.2174/0118715273453626260724060812","url":null,"abstract":"<p><p>Alzheimer's and Parkinson's diseases are devastating brain disorders. The complex pathophysiology of the diseases and the lack of effective treatments have left them almost unexplored and untreatable. One potential approach to PD and AD therapy development is through exosomes, a delivery system that can be translated from innovative delivery techniques into clinical use. These exosome-based therapeutics will require thorough testing, research-driven refinement of engineering methods, and collaboration among scientists, clinicians, and industry to develop exosome therapeutics for clinical use. This review explores the biological properties of exosomes, recent engineering advances to improve their therapeutic potential, and new methods to leverage their versatility for selective delivery of remedial agents to the brain. In addition, preclinical evidence demonstrates that exosomes can modulate amyloid-β aggregation, α-synuclein pathology, neuroinflammation, and mitochondrial dysfunction. Yet difficulties related to mass production, maintaining quality, and obtaining regulatory approvals to bring them into clinical practice remain significant limiting factors. The authors point out the therapeutic advantages and drawbacks of exosome-based drug delivery systems. Besides, it provides a roadmap for harnessing these methods effectively as medical interventions for Alzheimer's and Parkinson's disorders, thereby promoting more studies in the area. Finally, we outline a conceptual model for translating novel exosome-based delivery methods into clinically applicable treatment modalities for Alzheimer's and Parkinson's diseases, thereby encouraging continued exploration in this promising field of research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803099","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 Multifaceted Role of the P2X7 Receptor in Alzheimer's Disease: A Unifying Pathological Link.","authors":"Tejaswini Reddy Jeeru, Nagarjuna Palathoti, Gomathi Swaminathan","doi":"10.2174/0118715273460900260724035926","DOIUrl":"https://doi.org/10.2174/0118715273460900260724035926","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a neurodegenerative disorder that characterizes depletion of memory, cognition, and a change in behavioural patterns. There is no standard treatment that completely cures this prevalent disease. This review delves into the existing pathologies of AD, which include the Aβ plaques accumulation, neurofibrillary tangles and Lewy bodies formation, and the influence of the P2X7 receptor on cellular mechanisms of neuronal cells like microglial cells, astrocytes and oligodendrocytes and also its influence on pathways such as JAK2/STAT3, NGF signalling, (Transactive response DNA binding protein) TDP-43 Proteinopathy, Wnt/β-Catenin signalling, and FGF7/FGFR2/PI3K/Akt causing AD. It discusses the unifying role of the P2X7 receptor mediating these pathways that link to the occurrence and progression of AD. The role of the Purinergic receptor (P2X7 receptor), a ligand-gated ion channel activated by extracellular ATP, was examined across existing cellular mechanisms and possible pathways involved in AD, as well as the co-pathologies encompassed and their hypothetical relationship with the P2X7 receptor. Additionally, the current P2X7 receptor antagonists treating neurotoxicity are discussed along with existing pre-clinical and clinical data. This may further advance drug development by targeting the P2X7 receptor to mitigate AD across multiple mechanisms.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708918","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":"WNT Signaling in Alzheimer's Disease: Mechanisms, Pathological Implications, and Therapeutic Potential.","authors":"Dileep Kumar, Astik Manju Ashesh, Sanjana Gupta, Ajay Kumar, Sathiyanarayanan Lohidasan, Tahereh Jamshidnejad Tosaramandani","doi":"10.2174/0118715273455895260722103746","DOIUrl":"https://doi.org/10.2174/0118715273455895260722103746","url":null,"abstract":"<p><p>The WNT signaling pathway plays a significant role in various biological processes during embryonic development, childhood, and adulthood. It is involved in neurogenesis, synapse formation, and such cognitive processes as learning and memory in the CNS. Dysregulated WNT signaling is associated with cognitive decline, synaptic dysfunction, neuronal loss, and has been associated with diseases like leukemia and colorectal cancer. The studies show that WNT/β-catenin signaling affects the cellular, molecular, and metabolic mechanisms that promote disease progression. The WNT pathway is a potential therapeutic target because it helps maintain neuronal survival, supports the growth of new nerve cells, and enhances synaptic plasticity. WNT signaling is important for stem cell selfrenewal and differentiation. Research is being conducted on therapeutic methods targeting WNT signaling to treat neurological diseases and cancer. This review explores the connection between WNT signaling and the pathology of Alzheimer's disease. This review explores the role of WNT signaling in AD pathogenesis, with a focus on the Wnt/β-catenin pathway as a therapeutic target. It summarizes existing findings to demonstrate that WNT signaling is a context-dependent regulatory network in which a shift from protective canonical activity to dysregulated non-canonical and inflammatory pathways contributes to disease progression.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708667","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":"Endothelial-to-mesenchymal Transition at the Blood-brain Barrier: Molecular Mechanisms and Pathological Roles Across Brain Diseases.","authors":"Nur Iffah Ishak, Rosfaiizah Siran, Wan Nor I'zzah Wan Mohamad Zain, Nasibah Azme","doi":"10.2174/0118715273485479260721072747","DOIUrl":"https://doi.org/10.2174/0118715273485479260721072747","url":null,"abstract":"<p><p>Endothelial-to-Mesenchymal Transition (EndMT) is a significant contributor to Blood- Brain Barrier (BBB) dysfunction in various brain diseases. The majority of current therapies, aimed at reducing BBB dysfunction, focus on preventing inflammation or stabilizing tight junctions. In most cases, these therapies do not provide adequate or long-lasting vascular protection. Endothelial cells undergo phenotypic programming, losing their barrier-forming capacity and developing features of mesenchymal and extracellular matrix-producing cells as the disease progresses. The change leads to chronic vascular leakage, neuroinflammation, microvascular fibrosis, and dysfunctional neurovascular coupling. Several upstream stimuli, including inflammatory cytokines, TGF-β/BMP-Smad signaling, and oxidative damage, converge to drive EndMT within the distinctive, specialized environment of the brain endothelium. Ischemic stroke, multiple sclerosis, cerebral cavernous malformations, arteriovenous malformations, glioblastoma, brain metastasis, and Alzheimer's disease indicate that EndMT is not a rare or unique process but a shared and common pathologic process that may result in disease progression and eventual resistance to treatment. Recent single-cell and spatial transcriptomic data have shown that partial EndMT states exist and may be precursors to irreversible microvascular remodeling. It is necessary to identify therapeutic approaches that go beyond short-term stabilization of the BBB and target the molecular programs underlying the loss of endothelial identity. This review synthesizes mechanistic, disease-related, and therapeutic evidence indicating that EndMT is a leading cause of BBB failure and highlights therapeutic opportunities for targeting this endothelial plasticity in brain diseases.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611040","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":"Zolpidem vs. Emerging Hypnotics: Neuropsychiatric Effects and Ethical Considerations.","authors":"Tawqeer Shafi, Zora Singh, Puja Gulati, Shafqat Hussain Malik, Md Moidul Islam","doi":"10.2174/0118715273442470260706171716","DOIUrl":"https://doi.org/10.2174/0118715273442470260706171716","url":null,"abstract":"<p><strong>Introduction: </strong>Zolpidem is a widely used non-benzodiazepine hypnotic that is used as a treatment for insomnia due to its rapid onset and perceived safety. Nevertheless, rising clinical reports and post-marketing surveillance have identified serious neuropsychiatric adverse effects, such as hallucinations, perceptual disturbances, and complex sleep-related behaviors, such as sleep-driving and sleep-eating, as being frequent and often unnoticed by the patient. The consequences of such events can be severe personal injury and litigation. Regardless of these issues, there are few comparative data between zolpidem and newer hypnotics.</p><p><strong>Methods: </strong>A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science for studies published between 2020 and 2025.</p><p><strong>Results: </strong>Zolpidem was commonly linked to complex sleep acts, amnesia, and hallucinations, especially when in high dosage and when the patients had psychiatric comorbidities. On the contrary, some more recent ones, like orexin receptor antagonists, were less subject to such adverse effects, whereas the melatonin-based therapies were associated with positive safety profiles but lesser hypnotic efficacy. A number of case reports reported criminal charges in relation to zolpidem-induced altered states of consciousness.</p><p><strong>Conclusion: </strong>Zolpidem, despite its usefulness in the management of insomnia, has a relatively high likelihood of neuropsychiatric adverse effects, particularly among women, the elderly, psychiatric patients, and those who have undergone polypharmacy. Environmental risk-benefit evaluation must be performed cautiously and individually, prescribing zolpidem while taking into account patientspecific clinical and pharmacokinetic parameters.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521348","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":"Exosomes in Neurodegenerative Disorders: Isolation Strategies, Therapeutic Potential, and Clinical Trials.","authors":"Sourin Bhukta, Narahari N Palei, Vishakha Jaiswal, Anuradha Mishra, Prathap M","doi":"10.2174/0118715273459760260626154255","DOIUrl":"https://doi.org/10.2174/0118715273459760260626154255","url":null,"abstract":"<p><p>Exosomes represent a promising class of naturally produced nanoparticles that exist at the nanoscale and carry a negative surface charge under physiological conditions. These tiny membranebound vesicles are released by cells throughout the body and function as biological messengers, transporting various molecular cargos between cells and facilitating critical cell-to-cell communication pathways. Existing therapies for neurodegenerative disorders face two critical barriers: they cannot precisely target the affected brain areas, and the blood-brain barrier blocks most potential treatments from entering the brain. Exosomes offer a promising solution to these challenges. Unlike most synthetic drug delivery systems that struggle to penetrate the brain's protective barrier, these naturally derived nanocarriers exhibit an inherent capacity to traverse the blood-brain barrier. This unique property, combined with their capacity for efficient intracellular delivery of therapeutic payloads, positions exosomes as an exciting platform for transporting pharmaceutical agents to the affected neural tissues. Through strategic engineering and modification, these vesicles can be transformed into highly precise delivery vehicles capable of targeting specific organs, tissues, or even individual cell types. This review explores the therapeutic potential and drug delivery applications of exosomes in the management of major neurodegenerative disorders. This review provides an in-depth examination of exosome biogenesis, current isolation methodologies, and surface engineering strategies, while critically evaluating the strengths and limitations of each approach. In addition, this review summarizes the current preclinical models and provides an overview of ongoing clinical trials investigating exosome-based therapies for neurological disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551902","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":"Characteristics of Dysphagia Secondary to Ultrasound-guided Botulinum Injections for Cervical Dystonia.","authors":"Mikhal E Cohen, Yarden Cohen, Alfred Khazen, Iris Harari, Yosef Shechter, Ilana Israel, Alon Da-Lal, Roni Eichel, Gustavo Rajz, Gilad Yahalom","doi":"10.2174/0118715273442586260622111140","DOIUrl":"https://doi.org/10.2174/0118715273442586260622111140","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment with Botulinum Toxin (BT) is safe and effective. Nonetheless, dysphagia is perhaps the most common side effect of BT injections for Cervical Dystonia (CD). We aimed to characterize the population at risk of suffering from dysphagia following BT injections of cervical muscles.</p><p><strong>Methods: </strong>This is a retrospective observational study. We retrieved demographic and clinical data from the files of all patients diagnosed with CD who attended the Movement Disorders Unit at Shaare Zedek Medical Center during the years 2019 to 2025, and who were regularly treated with BT. The Sternocleidomastoids (SCMs) were injected either under Ultrasound Guidance (USg) or unguided, according to Anatomic Landmarks (AL). Thirty patients (18 females, 243 treatments) were included.</p><p><strong>Results: </strong>Dysphagia was reported in 12.6% of treatments, with a higher incidence in females compared to males (16.9% vs. 5.3%, p = 0.02). All reports of dysphagia (n = 25) were mild. Unguided SCM injections caused significantly less dysphagia than USg SCM injections (7.6% and 18.1%, respectively, p = 0.02). Among elderly patients (≥ 60 years), the incidence of dysphagia was also lower with unguided injections compared to US-guided injections (6.5% vs. 31.3%, p = 0.03).</p><p><strong>Discussion: </strong>Unguided BT injections into the Sternocleidomastoid (SCM) muscle resulted in a lower incidence of dysphagia compared to Ultrasound-guided (USg) injections. Additionally, elderly patients and women are at a heightened risk of experiencing dysphagia.</p><p><strong>Conclusion: </strong>Dysphagia appears to be a common side effect of US-guided BT injections, and it is possibly related to SCM injections. Caution should be particularly made in older females. We recommend treating the SCM muscles without guidance, particularly in older female patients.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457915","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":"Gut Microbiota in Neuroinflammation, Neurodegenerative Disorders, and Neuropsychiatric Disorders: A Comprehensive Narrative Review.","authors":"Smita Singh, Sumita Singh, Vishal Khandelwal, Ujjwal Bharti, Pranjal Kumar Singh","doi":"10.2174/0118715273455874260702045636","DOIUrl":"10.2174/0118715273455874260702045636","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Neurodegenerative and neuropsychiatric illnesses are characterized by neuroinflammation, which is driven by microglial activation, cytokine production, and breakdown of the blood-brain barrier (BBB). It is currently known that the gut microbiota plays an important role in modulating neuroimmune signaling, which in turn may trigger anxiety-like behaviors and depressive phenotypes through the microbiota-gut-brain axis. This review aims to integrate the most recent mechanistic knowledge on treatment strategies targeting the gut microbiota to modulate neuroinflammation. This review article discusses preclinical and clinical studies that investigated microbial composition, metabolite profiles, and host-microbe interactions involved in neuroinflammatory processes. However, special attention was given to signaling via the vagus nerves and bile acids, as well as to tryptophankynurenine metabolism and short-chain fatty acids (SCFAs). To examine the potential connection between the two, researchers used animal models such as germ-free animals and antibiotic-injected mice for fecal microbiota transplantation (FMT). This article defines dysbiosis as amplifying neuroinflammatory responses by altering microglial phenotypes, disrupting the blood-brain barrier, and triggering the production of pro-inflammatory cytokines. In contrast, microbiome diversity rehabilitation through the use of probiotics, prebiotics, synbiotics, and dietary modifications reduces neuroinflammatory markers and enhances cognitive and behavioral status. Clinical trials have shown considerable promise in diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), and depression. However, variability in treatment protocols, treatment resistance, and host-specific factors continue to pose significant challenges. This narrative review integrates mechanistic insights into microglial activation, cytokine signaling, blood-brain barrier regulation, vagal pathways, tryptophan metabolism, and short-chain fatty acids with emerging clinical evidence and therapeutic strategies, including probiotics, prebiotics, dietary modulation, and personalized microbiome-based interventions. Despite promising therapeutic potential, microbiome engineering faces important challenges, including safety concerns, lack of standardized intervention protocols, and substantial inter-individual variability in host-microbiome responses, which currently limit clinical translation. This review focuses on both neurodegenerative and neuropsychiatric disorders, examining shared neuroinflammatory mechanisms mediated by the gut-brain axis and evaluating microbiotatargeted therapeutic strategies across these disease categories. The review discusses both preventive strategies, including dietary modulation, prebiotics, and lifestyle-based microbiome interventions, as well as therapeutic approaches such as microbiota-targeted treatments aimed at mitigating neuroinflammation and disease pro","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431686","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}