Search Results (747)

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Neurodegenerative diseases (NDDs) such as Alzheimer’s, Parkinson’s, ALS, and Huntington’s pose a growing global challenge due to their complex pathobiology and aging demographics. Once considered as cellular debris, small extracellular vesicles (sEVs) are now recognized as active mediators of intercellular signaling in NDD progression. These nanovesicles (~30–150 nm), capable of crossing the blood–brain barrier, carry pathological proteins, RNAs, and lipids, facilitating the spread of toxic species like Aβ, tau, TDP-43, and α-synuclein. sEVs are increasingly recognized as valuable diagnostic tools, outperforming traditional CSF biomarkers in early detection and disease monitoring. On the therapeutic front, engineered sEVs offer a promising platform for CNS-targeted delivery of siRNAs, CRISPR tools, and neuroprotective agents, demonstrating efficacy in preclinical models. However, translational hurdles persist, including standardization, scalability, and regulatory alignment. Promising solutions are emerging, such as CRISPR-based barcoding, which enables high-resolution tracking of vesicle biodistribution; AI-guided analytics to enhance quality control; and coordinated regulatory efforts by the FDA, EMA, and ISEV aimed at unifying identity and purity criteria under forthcoming Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. This review critically examines the mechanistic roles, diagnostic potential, and therapeutic applications of sEVs in NDDs, and outlines key strategies for clinical translation. Full article

Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders remain underexplored. This review focuses on synthesizing the current knowledge of polyP in the context of central nervous system (CNS) diseases, highlighting how its involvement in key mitochondrial processes may influence neuronal survival and function. In particular, we examine recent evidence linking polyP to mechanisms relevant to neurodegeneration, such as the modulation of the mitochondrial permeability transition pore (mPTP), regulation of amyloid fibril formation, and oxidative stress responses. In addition, we analyze the emerging roles of polyP in inflammation and related cell signaling in CNS disorders. By organizing the existing data around the potential pathological and protective roles of polyP in the CNS, this review identifies it as a candidate of interest in the context of neurodegenerative disease mechanisms. We aim to clarify its relevance and stimulate future research on its molecular mechanisms and translational potential. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. Full article

Many neurodegenerative diseases are associated with immune system disorders, while neurodegenerative processes often occur in inflammatory conditions of the Central Nervous System (CNS). Cannabinoids exhibit significant therapeutic potential due to their dual ability to modulate both neural and immune functions. These compounds have a broad spectrum of action, allowing them to target multiple pathological mechanisms underlying neurodegenerative and inflammatory CNS diseases. The present review outlines the therapeutic potential of cannabinoids, with a focus on their anti-inflammatory properties, in the treatment of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, as well as inflammatory CNS disorders like multiple sclerosis and HIV-associated dementia. Full article

Pseudorabies virus (PRV) can infect a wide range of animal species, including swine and rodents. Infection in pigs is associated with significant economic losses in the global pork industry and is characterized by acute, often fatal disease, as well as central nervous system (CNS) invasion, which leads to neurological manifestations. Although PRV replication has been extensively characterized in certain murine neuronal cell lines such as Neuro-2a, the mechanisms underlying PRV-induced neuroinflammatory injury and necroptosis remain largely unclear. In this study, Kunming mice and mouse astrocytes (C8-D1A) were infected with PRV-GXLB-2013 at different doses to evaluate neurological injury and inflammatory responses. Given that the NF-κB/MLKL signaling pathway was found to be activated during PRV infection, a selective MLKL inhibitor, necrosulfonamide (NSA), was applied to investigate the role of necroptosis in PRV-induced neuroinflammatory damage. Mice infected with higher viral doses showed increased mortality, severe neurological symptoms, elevated brain inflammation, and pathological changes. In C8-D1A cells, PRV infection significantly upregulated inflammatory cytokines and key components of the NF-κB/MLKL pathway. Importantly, NSA treatment markedly reduced these inflammatory responses, mitochondrial damage, and cellular necrosis. Collectively, these findings suggest that PRV infection triggers neuroinflammatory injury through the activation of necroptosis and the NF-κB/MLKL signaling pathway. This study provides novel mechanistic insights into PRV-induced neurological damage and highlights potential therapeutic targets for intervention. Full article

Monomeric C-reactive protein (mCRP), derived from the dissociation of the native pentameric CRP (pCRP), has been implicated in the pathophysiology of various neurological conditions, particularly intracerebral hemorrhage (ICH) and neurodegenerative diseases. mCRP accumulates in the brain after hemorrhagic stroke, contributing to the formation of the metabolic penumbra and promoting inflammation. Recent studies have linked mCRP to the activation of microglia, endothelial cells, and complement pathways, which collectively intensify neuroinflammation and disrupt tissue repair mechanisms. Additionally, mCRP is associated with cognitive decline, particularly in ICH survivors, by promoting microvascular damage, neurodegeneration, and vascular instability. The presence of mCRP in distant regions of the brain, including the hypothalamus, suggests its potential role in spreading inflammation and exacerbating long-term neurological damage. This review synthesizes findings on the pathogenic role of mCRP in stroke and neurodegeneration, proposing that mCRP could serve as both a biomarker and a therapeutic target for improving outcomes in stroke patients. Emerging immunopharmacological strategies are being actively pursued to mitigate the pathogenic activity of mCRP, a potent pro-inflammatory effector implicated in a variety of immune-mediated and neuroinflammatory conditions. These approaches encompass the inhibition of native pentameric CRP dissociation into its monomeric isoform, the disruption of mCRP’s high-affinity interactions with lipid rafts and cell surface receptors involved in innate immune activation, and the enhancement of its clearance through mechanisms such as solubilization, opsonin-mediated tagging, and phagocytic engagement. Targeting these immunoregulatory pathways offers a compelling therapeutic framework for attenuating mCRP-driven inflammatory cascades in both systemic and CNS-specific pathologies. Full article

The gut microbiota constitutes a complex community of microorganisms (including bacteria, viruses, fungi, and protozoa) within the intestinal tract. Over the years, an increasing number of studies have highlighted the bidirectional communication between the gut microbiota and the central nervous system (CNS), a relationship commonly referred to as the “microbiota–gut–brain axis”. In particular, the crosstalk between the gut microbiota and the brain has been associated with the pathogenesis and progression of various CNS disorders. Phages, or bacteriophages, viruses that specifically infect bacteria, constitute the most abundant viral component within the gut microbiota. However, despite their abundance and significance in the gut microbial community, studies exploring the relationship between phages and the CNS remain surprisingly limited. This review examines the biological interplay between gut-resident phages and the CNS. Furthermore, we discuss the current literature linking phages to CNS-related pathologies. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

In neurons, mitochondria generate energy through ATP production, thereby sustaining the high energy demands of the central nervous system (CNS). Mitochondrial dysfunction within the CNS was implicated in the pathogenesis and progression of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, often involving altered mitochondrial dynamics like fragmentation and functional impairment. Accordingly, mitochondrial targeting represents an alternative therapeutic strategy for the treatment of these disorders. Current standard drug treatments present limitations due to adverse effects associated with their chronic use. Therefore, in recent years, nutraceuticals, natural compounds exhibiting diverse biological activities, have garnered significant attention for their potential to treat these diseases. It has been shown that these compounds represent safe and easily available sources for the development of innovative therapeutics, and by modulating mitochondrial function, nutraceuticals offer a promising approach to address neurodegenerative pathologies. We referred to approximately 200 articles published between 2020 and 2025, identified through a focused search across PubMed, Google Scholar, and Scopus using keywords such as “nutraceutical,” “mitochondrial dysfunction,” and “neurodegenerative diseases. The purpose of this review is to examine how mitochondrial dysfunction contributes to the genesis and progression of neurodegenerative diseases. Also, we discuss recent advances in mitochondrial targeting using nutraceuticals, focusing on their mechanisms of action related to mitochondrial biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability. Full article

It has been demonstrated that S100B actively participates in neuroinflammatory processes of different diseases of the central nervous system (CNS), such as experimental autoimmune encephalomyelitis (EAE), a recognized animal model for multiple sclerosis (MS). The inhibition of S100B activity using pentamidine and of S100B synthesis using arundic acid are able to determine an amelioration of the clinical and pathologic parameters of MS with milder and delayed symptoms. This study further goes in detail on the role of S100B, and in particular of astrocytic S100B, in these neuroinflammatory processes. To this aim, we used a model of S100B knockout (KO) mice. As expected, S100B protein levels were significantly reduced in the S100B KO mouse strain resulting in an amelioration of clinical and pathological parameters (clinical and morphological analyses). To dissect the potential mechanisms that could explain the role of S100B in the development of EAE, we sorted, cultured, and compared glial subpopulations (astrocytes, oligodendrocytes, and microglia) derived from S100B KO and wild type mice, through flow cytometric panels and ELISA. Glial cells were analyzed for proinflammatory molecules showing a significant reduction of TNFα protein in mice where S100B was silenced. To dissect the role of S100B in MS, we cultured astrocytes and microglial cells magnetically sorted and enriched from the brains of EAE-affected animals, both from KO and wild type animals. Both genetic silencing of S100B and pharmacological inhibition with S100B-targeting compounds demonstrated a direct impact on specific subpopulations of astrocytes (mainly), oligodendrocytes, and microglia. The present results further individuate astrocytic S100B as a key factor and as a potential therapeutic target for EAE neuroinflammatory processes. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative condition that is characterized by the accumulation of amyloid-β, the hyperphosphorylation of tau, and persistent neuroinflammation. However, these hallmarks alone do not fully capture the intricacies of AD pathology, thus necessitating the investigation of emerging mechanisms and innovative tools. Exosomes (nanoscale vesicles involved in cell communication and immune modulation) have emerged as pivotal cellular vehicles due to their dual role—both in the propagation of pathological proteins and the regulation of inflammatory responses. Furthermore, these vesicles have been demonstrated to play a crucial role in the mediation of the effects of microbiota-derived metabolites and the reflection of systemic influences such as dysbiosis, thereby establishing a link between the gut–brain axis and the progression of AD. A comprehensive narrative literature review was conducted using the following databases: ScienceDirect, Scopus, Wiley, Web of Science, Medline, and PubMed, covering studies published between 2015 and 2025. Inclusion and exclusion criteria were established to select research addressing exosomal biogenesis, their functional and diagnosis role, their therapeutic potential, and the emerging evidence on microbiota–exosome interplay in Alzheimer’s disease. Exosomes have been identified as integral mediators of intercellular communication, reflecting the molecular state of the central nervous system. These particles have been shown to promote the propagation of pathological proteins, modulate neuroinflammatory responses, and serve as non-invasive biomarkers due to their detectability in peripheral fluids. Advances in exosomal engineering and microbiome-based interventions underscore the potential for targeting systemic and CNS-specific mechanisms to develop integrative therapies for AD. Exosomes present a promising approach for the early diagnosis and personalized treatment of Alzheimer’s disease. However, methodological challenges and ongoing controversies, including those related to the influence of systemic factors such as dysbiosis, necessitate multidisciplinary research to optimize and standardize these strategies. Full article

The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases. Full article