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Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments, partly due to disruptions in neurotrophin signaling. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) play critical roles in neuronal survival, synaptic plasticity, and neuroprotection, yet their alterations across biofluids and brain regions in HD remain unclear. This study systematically reviewed and meta-analyzed human and rodent studies to quantify neurotrophin changes and explore moderating factors. Comprehensive searches of PubMed, Scopus, Web of Science, Embase, Google Scholar, and clinical trial registries were conducted up to December 2025. Studies reporting measurable BDNF, NGF, or NT-3 levels in HD patients or animal models were included. Data were extracted on neurotrophin type, sample source, subject characteristics, and measurement methods. Standardized mean differences were calculated using random-effects models, and meta-regression was applied to evaluate the effects of species, sex, sampling region, and analytical techniques. The results showed a significant decrease in neurotrophin levels in both peripheral biofluids and central brain regions in HD. The results for moderator analyses showed that species and sex significantly affected the magnitude of changes in ELISA-based studies, whereas molecular methods consistently detected reductions irrespective of these factors. No significant publication bias was identified. These findings highlight significant neurotrophic deficits in HD, highlight the importance of biological and methodological considerations in interpreting neurotrophin data, and suggest that peripheral neurotrophin measurements may serve as accessible biomarkers for disease progression. 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