Introduction: Mesenchymal Stem Cell (MSC) therapy is a promising strategy for modulating post-traumatic inflammation after Spinal Cord Injury (SCI), yet clinical responses vary widely. This case report introduces a unique, longitudinal biomarker-driven approach to track systemic molecular shifts after cell therapy. It adds to the scientific literature by establishing the MSC Response Index (MSCRI) to quantify how intervention timing alters the subacute and chronic neuroinflammatory landscape. Case Presentation: Two patients with traumatic SCI underwent autologous bone marrow-derived MSC (BM-MSC) transplantation at different time points post-injury (Day 46 vs. Day 73). Circulating cytokines, chemokines, growth factors (including IL-10, IL-1Ra, IL-8, MCP-1, VEGF), and neuromarkers (S100, GFAP, pNF-H) were longitudinally monitored in serum and cerebrospinal fluid. Regarding clinical outcomes, both patients tolerated the transplantation well, achieved systemic stabilization, and were discharged to external rehabilitation facilities. Patient 1 (treated on Day 46) exhibited a robust, sustained early anti-inflammatory response with upregulation of IL-10/IL-1Ra and suppression of pro-inflammatory chemokines. Conversely, Patient 2 (treated on Day 73) showed a limited early response and a subsequent shift toward a pro-inflammatory profile at 6 months. Conclusion: Our findings primarily indicate that the therapeutic window shapes the immunomodulatory potential of BM-MSCs in SCI. Administration during the subacute phase allows for effective, sustained anti-inflammatory shifts, whereas early chronic intervention yields limited molecular effects. Furthermore, the proposed MSCRI provides a simple framework for quantifying inflammatory balance and supporting patient stratification, even when long-term physical rehabilitation occurs externally.
Objective: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by nigrostriatal dopaminergic neuronal loss, neuroinflammation, oxidative stress, and motor dysfunction. Current therapies mainly provide symptomatic relief, whereas effective disease-modifying strategies remain limited. Yindan Xinnaotong soft capsule (YDXNT), a multi-component Chinese patent medicine, has shown neuroprotective potential, but its pharmacological effects in PD remain insufficiently understood. This study aimed to investigate the neuroprotective effects of YDXNT and identify signaling pathways potentially involved in its actions against experimental PD-related pathology. Methods: Network pharmacology was used to identify candidate bioactive compounds, therapeutic targets, and enriched pathways of YDXNT in PD. Molecular docking was performed to predict interactions between representative compounds and core targets. The predicted mechanisms were further evaluated in vivo using MPTP-induced parkinsonian mice and in vitro using MPP+-treated BV-2 microglial cells. Behavioral testing, TH and Iba-1 staining, ELISA, RT-qPCR, and Western blotting were used to assess motor function, dopaminergic injury, microglial activation, neurotrophic factors, and pathway-related molecular changes. Results: Seven representative compounds—β-sitosterol, cryptotanshinone, isogoycyrol, isorhamnetin, kaempferol, luteolin, and quercetin—were prioritized as candidate bioactive constituents. PI3K, AKT, MDM2, and p53 were identified as core pathway-related targets, and molecular docking predicted favorable compound–target interactions, with binding energies below −6 kcal/mol. YDXNT improved motor performance, preserved TH-positive neurons and striatal fibers, and reduced Iba-1-positive microglial activation in MPTP-treated mice. High-dose YDXNT also increased BDNF, GDNF, and CDNF levels. In animal tissues and BV-2 cells, YDXNT increased PI3K and AKT phosphorylation and MDM2 expression while reducing p53 expression. Discussion: These findings suggest that YDXNT may exert neuroprotective effects through coordinated regulation of dopaminergic neuronal integrity, microglial activation, neurotrophic support, and cell-survival signaling. The convergence of network pharmacology, molecular docking, and experimental findings supports the possible involvement of the PI3K/AKT/MDM2/p53 signaling axis; however, the current evidence demonstrates association rather than pathway causality, and direct target engagement requires further validation. Conclusion: YDXNT ameliorates experimental PD-related pathology through multi-component and multi-target actions associated with the regulation of the PI3K/AKT/MDM2/p53 signaling axis, supporting its further investigation as a potential neuroprotective strategy for PD.
Dopamine is a critical neurotransmitter involved in the regulation of motor control, cognition, reward processing, motivation, and neuroendocrine functions. Increasing evidence indicates that disturbances in dopaminergic neurotransmission contribute significantly to the pathogenesis of major neurodegenerative disorders, particularly Parkinson’s Disease (PD) and Alzheimer’s Disease (AD). The dopaminergic system comprises specialized neuronal populations, dopamine receptors, and transporter proteins that collectively maintain synaptic dopamine homeostasis and neuronal signaling. Degeneration of dopaminergic neurons is a hallmark of PD, whereas emerging studies suggest that impaired dopamine signaling also plays an important role in the cognitive and behavioral deficits associated with AD. This review summarizes current knowledge regarding the involvement of dopaminergic pathways in neurodegeneration, with emphasis on receptor subtypes, dopamine transporter function, and neuronal vulnerability. Furthermore, it discusses established therapeutic interventions, including dopamine receptor agonists and other dopaminergic modulators, highlighting their clinical benefits and limitations. Recent advances in the field, such as biased receptor ligands, gene-based therapies, stem cell-mediated regeneration, and nanoparticle-assisted drug delivery systems, are also evaluated for their potential to enhance therapeutic efficacy and target specificity. In addition, commonly used experimental models for investigating dopaminergic dysfunction and disease progression are reviewed. Despite substantial progress, several translational challenges continue to hinder the development of disease-modifying treatments. A deeper understanding of dopaminergic signaling mechanisms and their interactions with neurodegenerative processes may facilitate the identification of novel therapeutic targets. Future strategies should focus not only on symptomatic management but also on slowing or preventing disease progression through precise modulation of dopaminergic networks.
Background: Migraine is one of the most common and debilitating neurological diseases that impacts quality of life. Despite available preventive treatments, many patients face insufficient relief or side effects. The role of Calcitonin Gene-Related Peptide (CGRP) in migraine pathophysiology has prompted the development of monoclonal antibodies targeting CGRP or its receptors. This review examines the role of CGRP in the treatment and prevention of episodic and chronic migraine. It is also intended to help develop specific treatments that could result in better outcomes for those suffering from migraines, especially those with chronic migraines. Methods: A comprehensive literature review was conducted in accordance with the PRISMA guidelines, focusing on studies evaluating monoclonal antibodies targeting CGRP or its receptor in adults with chronic or episodic migraine. Data on treatment efficacy, safety, and patient-reported outcomes were analyzed. Results: The analysis found that monoclonal antibodies targeting CGRP effectively decrease the severity and frequency of migraines in both chronic and episodic migraine patients. Participants reported improvements in quality of life and reduced migraine-related debility. The safety profile was generally favorable, with mild-to-moderate injection-site reactions as the most common adverse events. Serious side effects were rare, and the rate of discontinuations due to adverse effects was low. Discussion: The literature highlights the need for personalized treatment strategies tailored to individual patient profiles, emphasizing the critical role of patient selection in optimizing treatment outcomes. Ongoing research is vital for improving these therapies and evaluating their wider applicability across various patient populations. Conclusion: Monoclonal antibodies targeting CGRP provide an effective, well-tolerated option for preventing both chronic and episodic migraines. These treatments offer a solution for patients who do not respond well to traditional therapies. Additional research is needed to evaluate long-term safety, cost-effectiveness, and optimal patient selection for these new therapies.
Abstract: More than fifty million individuals worldwide are experiencing neurodegenerative disorders, which include Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and frontotemporal dementia. These disorders have a significant role in the gradual degradation of cognition and motor skills. Most current treatment approaches have little effect on changing the course of the disease and are largely symptomatic. Psilocybin, a naturally occurring tryptamine alkaloid from psilocybin mushrooms, has become a promising medicinal agent because of its hallucinogenic, neuroprotective, and neuroplastic properties. After being metabolically transformed into its active form, psilocin, it primarily activates serotonin 5-HT2A receptors. This modulates glutamatergic neurotransmission and neurotrophic signaling pathways such as BDNF/TrkB and mTOR, which regulate synaptic remodeling, dendritic complexity, neurogenesis, neuroinflammatory response, and default mode network connectivity, all of which are linked to depression and dementia. Preclinical research studies demonstrate that psilocybin increases hippocampal plasticity, restores dendritic complexity, lowers proinflammatory cytokine levels, and promotes fear extinction in experimental models of stress, ischemic stroke, and neurodegeneration. Emerging clinical studies also indicate that individuals with moderate cognitive impairment, early-onset Alzheimer’s disease, and Parkinson’s disease may see long-term decreases in anxiety and depression as well as improvements in cognitive function, frequently after a single dose administration. Additionally, psilocybin has demonstrated promise in treating mental comorbidities that often accompany neurodegenerative illness, such as treatment-resistant depression, drug use disorders, and obsessive-compulsive disorder. However, there are still significant obstacles to overcome, such as optimizing dosing schedules, assessing safety issues such as temporary perceptual abnormalities and cardiovascular consequences, and translating preclinical results into extensive phase -III clinical studies. This review incorporates the most recent data on psilocybin’s chemistry, pharmacology, metabolism, and mechanistic actions; it highlights the drug’s therapeutic potential across a variety of neurodegenerative diseases and emphasizes the necessity of carefully planned randomized controlled trials to determine clinical efficacy, long-term safety, and its place in multimodal treatment approaches.
