Clinical and Experimental Neuroimmunology最新文献

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV-1 infection. The biased geographic distribution of HTLV-1-infected individuals facilitated the early identification of a causal relationship between HTLV-1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV-1 with EBV, focusing on their shared strategies for establishing long-term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.

Idiopathic inflammatory myopathies (IIMs), or myositis, are a heterogeneous group of autoimmune diseases affecting skeletal muscle and other organs. Recent research has revealed the important role of interferons (IFNs) in the pathogenesis of IIMs. This review summarizes the three types of IFNs and their functions in the immune system, focusing on their association with different IIM subtypes. Dermatomyositis (DM) is strongly associated with Type I IFNs. In contrast, inclusion body myositis (IBM), polymyositis with mitochondrial pathology (PM-mito), and anti-synthetase syndrome (ASyS) are predominantly associated with Type II IFN. This review explores the molecular mechanisms underlying these associations and their impact on muscle function. In addition, the potential of the IFN signaling pathway as a therapeutic target for IIMs will be discussed. Several clinical trials are currently underway or planned that target the IFN pathway using JAK inhibitors and monoclonal antibodies against Type I IFNs. JAK inhibitors have shown promise in treating DM, particularly in refractory cases. However, more research is needed to fully understand their efficacy and safety profiles in IIMs. The review concludes by highlighting the importance of ongoing research in this area and the potential for new targeted therapies in treating IIMs.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to hallmark motor symptoms such as bradykinesia, tremors, and rigidity. Emerging evidence suggests that the dysregulation or aberrant expression of long noncoding RNAs (lncRNAs) plays a critical role in the pathogenesis of PD by activating the inflammasome, either directly or via oxidative stress. Aberrant lncRNA expression has been linked to alterations in genes related to oxidative stress, causing an imbalance between reactive oxygen species (ROS) and antioxidant defenses. This imbalance contributes to mitochondrial dysfunction and neuronal damage. The NLRP3 inflammasome is a multiprotein complex comprising a sensor protein (eg, NLRP3), an adaptor protein (ASC), and an effector protein (caspase-1). Its activation involves priming via NF-κB signaling and is triggered by ROS, mitochondrial dysfunction, death-associated molecular patterns, or extracellular ATP. Once activated, the inflammasome promotes the cleavage and maturation of the proinflammatory cytokines IL-1β and IL-18, amplifying neuroinflammation and leading to neurodegeneration in PD. Crosstalk between dysregulated lncRNAs, ROS production, and inflammasome activation creates a vicious cycle of neuroinflammation and neurodegeneration, exacerbating PD progression. This review explores the molecular mechanisms linking lncRNA dysregulation to inflammasome activation in PD, either directly or through oxidative stress. It also highlights key lncRNAs involved in these processes. Furthermore, potential therapeutic strategies targeting these pathways, such as antioxidants, lncRNA modulators, and inflammasome inhibitors, offer promising avenues to mitigate neuroinflammation and slow neurodegeneration in PD.