Neural Regeneration Research最新文献

JOURNAL/nrgr/04.03/01300535-202606000-00075/figure1/v/2026-02-11T151048Z/r/image-tiff Demyelinating diseases of the central nervous system are common, yet few effective strategies for myelin repair and remyelination are available. An increasing number of studies highlight the role of microRNAs (miRNAs) as key regulators of demyelination. miRNA mimics and inhibitors, which are currently in preclinical development, have shown promise as novel therapeutic agents. However, the mechanisms by which they protect myelin are not fully understood. Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis , we investigated alterations in miRNA expression in the mouse brain. Our findings revealed a significant early-stage increase in the levels of miR-200, particularly miR-200a and miR-200c. Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis -infected mice. Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog (PTEN) and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway, as confirmed by double luciferase reporter assay and western blotting. Additionally, in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival. Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways. Furthermore, our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.

Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases. Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6 (DNAJB6) chaperone is particularly interesting, when it comes to preventing amyloidogenic proteins from aggregating. It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington's disease. Likewise, it can suppress aggregation of α-synuclein in models of Parkinson's disease and other synucleinopathies. Finally, it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer's disease and other tauopathies as well. We believe there is yet much to learn about the protective role of DNAJB6 in the brain, but this focused review summarizes, what we know so far of this chaperone. It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70, with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo . Moreover, recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed. Finally, we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.

The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways, with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline. Insulin resistance impairs neuronal metabolism and synaptic function, fostering neurodegeneration as observed in Alzheimer's disease and Down syndrome. Indeed, Down syndrome, characterized by the triplication of the APP gene, represents a valuable genetic model for studying early-onset Alzheimer's disease and accelerated aging. Building on the link between metabolic dysfunctions and neurodegeneration, innovative strategies addressed brain insulin resistance as a key driver of cognitive decline. Intranasal insulin has shown promise in improving cognition in early Alzheimer's disease and type 2 diabetes, supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration. However, insulin-based therapies risk desensitizing insulin signaling, potentially worsening the disease. Incretins, particularly glucagon-like peptide 1 receptor agonists, offer neuroprotective benefits by enhancing insulin sensitivity, metabolism, and synaptic plasticity while reducing oxidative distress and neuroinflammation. This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance, mitochondrial dynamics (including their roles in energy metabolism), and oxidative distress regulation, as these are pivotal in both Alzheimer's disease and Down syndrome. By addressing these interconnected mechanisms, innovative treatments may emerge for both metabolic and neurodegenerative disorders.

JOURNAL/nrgr/04.03/01300535-202606000-00080/figure1/v/2026-02-11T151048Z/r/image-tiff Peripheral nerve injury is a complex condition presenting significant clinical treatment challenges due to the limited regenerative capacity of peripheral nerves. Nerve conduits have been seen as a promising strategy to overcome the shortage of other treatment options (e.g., nerve graft). However, nerve regeneration occurs within a complex environment, and elaborate modulation is needed to meet repair requirements. The aim of this study was to investigate and explore a multifunctional nerve conduit with reactive oxygen species clearing, immune modulation to reshape the regenerative environment, and topographic cues and electrical signals to guide nerve growth. We developed an electroactive nerve guidance conduit composed of polylactic-glycolic acid and carbon nanotubes with an oriented structure using electrospinning and modified it with mussel-inspired polydopamine combining neurotrophin-3. The resulting nerve scaffold exhibited favorable orientation, electrical conductivity, and mechanical properties. Continuous release of neurotrophin-3 from the nerve conduit supported nerve regeneration throughout the repair process. In vitro assessments confirmed the cytocompatibility, reactive oxygen species scavenging, and immune regulation capabilities of the nerve scaffolds. In a rat sciatic nerve defect model, the nerve scaffolds effectively prevented muscle atrophy and promoted nerve regeneration and functional recovery over a 12-week period. These findings suggest that polydopamine-modified, electroactive, oriented nerve guidance conduits with multiple bioactive functions hold great promise for the repair of peripheral nerve injuries.