医学最新文献

Neurodegenerative diseases are prevalent conditions that greatly impact human health. These diseases are primarily characterized by the progressive loss and eventual death of neuronal function, although the precise mechanisms underlying these processes remain incompletely understood. Iron is an essential trace element in the human body, playing a crucial role in various biological processes. The maintenance of iron homeostasis relies on the body's intricate and nuanced regulatory mechanisms. In recent years, considerable attention has been directed toward the relationship between dysregulated iron homeostasis and neurodegenerative diseases. The regulation of iron homeostasis within cells is crucial for maintaining proper nervous system function. Research has already revealed that disruptions in iron homeostasis may lead to ferroptosis and oxidative stress, which, in turn, can impact neuronal health and contribute to the development of neurodegenerative diseases. This article primarily explores the intimate relationship between iron homeostasis and neurodegenerative diseases, aiming to provide novel insights and strategies for treating these debilitating conditions.

The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions, including regulating the inflammatory cascade in various autoimmune and inflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, diabetes, inflammatory skin diseases, joint inflammation, and cancer. Although the function of the interleukin-17 family has attracted increasing research attention over many years, the expression, function, and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood. Currently, the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases, with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice. Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated. This review first summarizes the recent advancements in understanding the physicochemical properties, physiological functions, cellular origins, and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family. Subsequently, the function of interleukin-17 in various immune diseases is discussed, and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives. Then, the current status of targeted interleukin-17 therapy is summarized, and the effectiveness and safety of targeted interleukin-17 therapy are analyzed. Finally, the clinical application prospects of targeting the interleukin-17 pathway are discussed.

The capacity of the central nervous system for structural plasticity and regeneration is commonly believed to show a decreasing progression from "small and simple" brains to the larger, more complex brains of mammals. However, recent findings revealed that some forms of neural plasticity can show a reverse trend. Although plasticity is a well-preserved, transversal feature across the animal world, a variety of cell populations and mechanisms seem to have evolved to enable structural modifications to take place in widely different brains, likely as adaptations to selective pressures. Increasing evidence now indicates that a trade-off has occurred between regenerative (mostly stem cell-driven) plasticity and developmental (mostly juvenile) remodeling, with the latter primarily aimed not at brain repair but rather at "sculpting" the neural circuits based on experience. In particular, an evolutionary trade-off has occurred between neurogenic processes intended to support the possibility of recruiting new neurons throughout life and the different ways of obtaining new neurons, and between the different brain locations in which plasticity occurs. This review first briefly surveys the different types of plasticity and the complexity of their possible outcomes and then focuses on recent findings showing that the mammalian brain has a stem cell-independent integration of new neurons into pre-existing (mature) neural circuits. This process is still largely unknown but involves neuronal cells that have been blocked in arrested maturation since their embryonic origin (also termed "immature" or "dormant" neurons). These cells can then restart maturation throughout the animal's lifespan to become functional neurons in brain regions, such as the cerebral cortex and amygdala, that are relevant to high-order cognition and emotions. Unlike stem cell-driven postnatal/adult neurogenesis, which significantly decreases from small-brained, short-living species to large-brained ones, immature neurons are particularly abundant in large-brained, long-living mammals, including humans. The immature neural cell populations hosted in these complex brains are an interesting example of an "enlarged road" in the phylogenetic trend of plastic potential decreases commonly observed in the animal world. The topic of dormant neurons that covary with brain size and gyrencephaly represents a prospective turning point in the field of neuroplasticity, with important translational outcomes. These cells can represent a reservoir of undifferentiated neurons, potentially granting plasticity within the high-order circuits subserving the most sophisticated cognitive skills that are important in the growing brains of young, healthy individuals and are frequently affected by debilitating neurodevelopmental and degenerative disorders.

JOURNAL/nrgr/04.03/01300535-202605000-00035/figure1/v/2025-10-21T121913Z/r/image-tiff The remodeling of axonal connections following injury is an important feature driving functional recovery. The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers. While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord, the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear. As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input, we investigated in this study the plastic potential of glutamatergic (vGlut2) and GABAergic (vGat) fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus, two nuclei important for locomotor function. Using a combination of viral tracing, chemogenetic silencing, and AI-based kinematic analysis, we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury, a period prone to neuronal remodeling. We demonstrate that, in this time frame, while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury, vGat-positive fibers are rather unresponsive to injury. We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery. Using kinematic analysis, we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery. Overall, our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.

Alzheimer's disease is the most common type of cognitive disorder, and there is an urgent need to develop more effective, targeted and safer therapies for patients with this condition. Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation. As an emerging therapeutic approach, deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease. Here, we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research. In clinical studies, the most commonly targeted sites include the fornix, the nucleus basalis of Meynert, and the ventral capsule/ventral striatum. Basic research has found that the most frequently targeted areas include the fornix, nucleus basalis of Meynert, hippocampus, entorhinal cortex, and rostral intralaminar thalamic nucleus. All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated. Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms, including reducing the deposition of amyloid-β, activation of the cholinergic system, increasing the levels of neurotrophic factors, enhancing synaptic activity and plasticity, promoting neurogenesis, and improving glucose metabolism. Currently, clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient. In the future, it is essential to focus on translating preclinical mechanisms into clinical trials. Furthermore, consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease, including cognitive function, neuropsychiatric symptoms, quality of life and changes in Alzheimer's disease biomarkers. Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows, such as the prodromal and even the preclinical stages of Alzheimer's disease. Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.