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Astroglia, often called as astrocytes, play a crucial role in protecting neurons and preserved the neurophysiological functions. Astrocytes' dysfunction contributes to numerous neurological disorders. Astrocytes are involved in the regulation of oxidative stress and inflammatory process within Central nervous system. Developments in specific transcriptomic and genomics have initiated the discovery of new mechanisms governing astrocyte during oxidative and inflammatory process. Despite the advancements in existing diagnostic and therapeutic methods like targeted ultrasound and NPs mediated administration, these methods still pose risks and have drawbacks. Aptamers, artificial single stranded oligonucleotides have the ability to specific target cells and exhibit strong binding affinity and enhance the administration of therapeutic agents. Research over the last few years has demonstrated that the ability to target specific molecules/intermediates such as reactive oxygen species, interleukins, tumor necrotic factor, vascular endothelial growth factor, brain-derived neurotrophic factor and penetrate the blood brain barrier makes aptamers ideal candidates for addressing the oxidative and inflammatory intermediaries within astrocytes. Present review explores the emerging applications of aptamers in cytoprotection specially focus on their potential to combat oxidative stress and inflammation in astrocytes. We also discuss the capability of aptamers as cell specific molecular probes for advancing tailored diagnostic and therapeutic interventions. Present article also addresses future directions and significant issues. Show less

Acetylation, a key post-translational modification, is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Among HDACs, HDAC6-a class II deacetylase with predominant cytoplasmic localization-plays a unique role in cellular processes that extend beyond histone modification. It is ubiquitously expressed throughout the central and peripheral nervous systems and is integral to key physiological functions including protein quality control, autophagy, mitochondrial transport, and oxidative stress responses. Notably, under pathological conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, and peripheral nerve injury, HDAC6 undergoes nuclear translocation and contributes to epigenetic dysregulation by modulating the transcription of genes such as brain-derived neurotrophic factor, thereby impairing synaptic integrity and function. This dual role-cytoplasmic in protein homeostasis and nuclear in transcriptional regulation-highlights the HDAC6 paradox in neurological disorders. This review summarizes recent understanding of HDAC6's structure, expression, and functions within the nervous system, and discuss how targeting HDAC6 with selective inhibitors offers a promising therapeutic strategy for mitigating neurological disease pathogenesis. The goal is to provide insights that bridge HDAC6's roles in protein quality control and epigenetic regulation, fostering further exploration of HDAC6 inhibition in neurologic therapeutics. Show less

Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. Show less

Fujian Tablets (FJT), a traditional Chinese medicinal (TCM) preparation, has been clinically used in the rehabilitation of neurological disorders related to ischemic brain injury in the context of TCM theory. However, its molecular mechanism underlying the promotion of post-ischemic stroke motor function recovery, especially via regulating corticospinal tract (CST) remodeling-a key structure for motor control-remains unelucidated. This study aimed to investigate the effect of FJT on CST remodeling in the denervated hemisphere and motor function recovery in middle cerebral artery occlusion (MCAO) rats, and to explore its potential mechanism by focusing on the balance between precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF), which is tightly regulated by BDNF-cleaving enzymes (Pcsk1 and Furin). The MCAO rat model was established using the intraluminal filament method. Model rats were randomly divided into four groups: MCAO model group, FJT low-dose group, FJT medium-dose group, and FJT high-dose group. Motor function was evaluated by Catwalk gait analysis (assessing average speed, step length, and standing time). CST remodeling and conduction efficiency were determined via biotinylated dextran amine (BDA) neural tracing and motor evoked potential (MEP) detection, respectively. The mRNA and protein expressions of BDNF, cleaving enzymes (Pcsk1, Furin), and related receptors (TrkB, p75NTR, Sortilin) in brain tissues were measured using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. BDNF silencing experiment was performed to verify the role of BDNF in FJT-induced effects. Additionally, in vitro neuronal culture was used to observe the effects of FJT, exogenous mBDNF, and Pcsk1/Furin inhibitors on neuronal growth. Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters increasing average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26 % increase in BDA-positive nerve fibers and elevated growth-associated protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors. Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters, increasing the average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26% increase in BDA-positive nerve fibers and elevated Growth-Associated Protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors. Show less

Neurological disorders cause over 11 million deaths annually worldwide, highlighting the urgent need for new therapeutic strategies to improve current treatment outcomes. Nerve growth factor (NGF) is a key regulator of neuronal survival, and modifying mesenchymal stem cells (MSC) to enhance their neurotrophic activity is a promising therapeutic strategy. However, the broader molecular consequences of NGF overexpression in MSC remain unclear. This study examined how NGF overexpression affects neurotrophin secretion and apoptosis-related protein expression in Wharton's jelly MSC (WJ-MSC). WJ-MSC were lentivirally transduced to overexpress NGF and differentiated for 12 days. NGF, BDNF, TrkA, TrkB, IL-13, and TNF-α were quantified using ELISA (n = 3 biological replicates; assays in duplicate). Thirty-five apoptosis-related proteins were assessed using the Proteome Profiler Human Apoptosis Array (assays in duplicate). Data were analyzed using one-way ANOVA or multiple t-test. NGF overexpression increased extracellular NGF (↑∼220 %, p < 0.0001) and reduced BDNF secretion (↓∼35 %, p < 0.05). Soluble phosphorylated TrkA/TrkB increased significantly in supernatants (↑30-60 %, p < 0.05). IL-13 rose modestly without statistical significance, and TNF-α remained undetectable. Early proteome changes showed upregulation of pro-apoptotic proteins (p21 ↑97 %, phospho-p53 ↑30 %) with concurrent reductions in anti-apoptotic markers (BCL2 ↓66 %, HSP60 ↓58 %). After 12 days, the apoptotic profile remained predominantly pro-apoptotic, despite selective increases in BCLXL (↑92 %), clusterin (↑102 %), and survivin (↑38 %) indicating only partial compensatory responses. NGF overexpression enhances neurotrophin-related signaling but produces a sustained pro-apoptotic shift in WJ-MSC, suggesting limited benefit for cell survival. These findings require confirmation using functional apoptosis assays and in vivo models. Show less