Year: 2026
Type: editorial
Abstract: such as synaptic dysfunction and network failure.The relevance of this field lies in its ability to bridge finely regulated cellular mechanisms with higher-order dysfunction and therapeutic strategies. This conceptual framework is particularly critical for several neurodegenerative conditions, in which decades of research have yet to yield effective disease-modifying treatments. A recurring theme emerging from contemporary neuroscience is the loss of homeostatic balance: when molecular control mechanisms governing ion channel activity, gene regulation, protein stability, or immune responses are disrupted, the CNS progressively shifts toward maladaptive plasticity and neurodegeneration. Understanding how these alterations converge at the synaptic and circuit levels is therefore essential for translating basic discoveries into meaningful clinical advances. Within this context, the articles included in this Research Topic provide examples how diverse molecular players, experimental models, conceptual frameworks and computational methods can be integrated to clarify disease mechanisms and identify new therapeutic opportunities.A recurring message across contemporary studies, highlighted throughout this Research Topic, is the importance of integrating diverse experimental models and diseases to accelerate discovery and translation.For example, Ding et al. in this Research Topic showed that memory processes and neuronal development can be influenced by the transmembrane protein DPP6, which acts as a critical modulator of the potassium channel (Kv4.2) function, with its dysregulation implicated not only in Alzheimer's disease but also in motor disorders such as amyotrophic lateral sclerosis.To achieve progress enabling clinical human application, bridging research across species has significant importance. In this context, Yadav et al. illustrated how simple organisms such as the nematode Caenorhabditis elegans provide powerful platforms for rapidly interrogating complex genetic mutations and for screening candidate pharmacological interventions. Accordingly, they showed how this model can be effective in studying a group of neglected genetic disorders, namely GNAO1 encephalopathies, primarily occurring due to de novo mutations in the Gao protein-encoding gene.To enable clinical translatability, previously established approaches are increasingly complemented by more advanced inducible cell type-specific murine models and human clinical investigations. In this context, Kawato As reported by Kocakusak et al., growing attention has been directed toward tRNA-derived fragments, small molecules playing essential roles in maintaining cellular homeostasis, in disease pathogenesis. Interestingly, these fragments also function as epigenetic and post-translational regulators rather than passive degradation products, positioning them as promising biomarkers and potential therapeutic targets for neurological and psychiatric conditions, including Parkinson's disease and epilepsy. This epigenetic complexity is further reviewed by Xu et al., which present the innovative concept of the retina as an extension of the CNS, detailing the changes in DNA methylation patterns in diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma. The exploration is further extended from the retina to the brain, where DNA methylation not only guides neuronal development but also serves as a molecular "clock" and a diagnostic window for disorders such as schizophrenia and autism.Together with pharmacological and molecular advances, contemporary neuroscience increasingly recognizes the contribution of lifestyle factors and holistic approaches to brain health. Canonichesi et al. showed that physical exercise improves sleep quality in synucleinopathies such as Parkinson's disease, thereby facilitating the clearance of toxic α-synuclein aggregates. In parallel, Gonçalves Silva et al. reported that environmental enrichment, through sensory and cognitive stimulation, can modulate autophagy, the brain's intrinsic cellular maintenance system, under adverse conditions. Complementing these findings, Yu et al. highlighted how compounds derived from traditional Chinese medicine may regulate microglia-driven neuroinflammation, promoting phenotypic shifts toward neuroprotective states that support neuronal repair and functional recovery in Alzheimer's disease.Taken together, these converging lines of evidence convey a clear message: the future of neuroscience and medicine lies in the effective translation of fundamental discoveries, ranging from protein interactions and RNA fragments to regulated cell death pathways, into targeted and integrated therapeutic strategies. The convergence of basic molecular research, experimental models, advanced imaging techniques, novel delivery methods, pharmacological and non-pharmacological interventions represents the most promising path forward for addressing neurological and psychiatric disorders that pose an increasing global burden, reaffirming that scientific research is not an abstract attempt but a critical driver of meaningful improvements in patients' quality of life.
Authors: Alessandro Tozzi, Chao Deng, Dirk M. Hermann
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7153887779
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