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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

Brain-derived neurotrophic factor (BDNF) is a neurotrophin with crucial roles in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. The pleiotropic functions of BDNF require stringent spatiotemporal control of its expression, making BDNF one of the most thoroughly studied activity-regulated genes. Over the years, substantial evidence has accumulated, providing insights into BDNF gene structure, numerous mRNA variants, their different localization patterns and translational efficiencies, as well as the functions of the BDNF protein in different tissues. This review aims to summarize the current understanding of the mechanisms governing BDNF expression at transcriptional, posttranscriptional, and translational levels, offering an integrated perspective of BDNF regulation. Show less

The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential. Show less

Brain-derived neurotrophic factor (BDNF) is a key neurotrophin due to its role in neuron process outgrowth, plasticity, and neuronal survival. Aerobic exercise can induce BDNF release and may ultimately maximize post-stroke recovery. This study aimed to determine if a program of moderate-to-high-intensity aerobic exercise increased concentrations of BDNF in subacute stroke survivors compared to usual care. A parallel-group, RCT was undertaken in people with subacute stroke undergoing rehabilitation. Participants were randomly allocated to usual care (control group) or usual care plus an 8-week program of moderate-high intensity treadmill walking (3 x 30 min sessions per week) (experimental group). Serum BDNF was collected by blinded assessors at baseline (Week 0), at the end of the intervention period (Week 8), and at 6 months follow up (Week 26). Sixty-seven participants ( As concentrations of BDNF increased immediately after a program of aerobic exercise, this may present a potential neurobiological mechanism to enhance recovery after stroke. Show less

Brain-derived neurotrophic factor (BDNF) is a neurotrophin important for neuronal survival and synaptic plasticity that also plays a role in metabolic regulation (energy homeostasis and appetite control). Lower circulating BDNF levels have been associated with obesity, metabolic risk factors, and poorer cognitive and mental health outcomes, whereas higher levels are linked to more favorable profiles. In this study we sought to systematically evaluate the effects of dietary weight-loss interventions on circulating BDNF levels in adults with overweight or obesity. A comprehensive literature search of PubMed, Web of Science, Scopus, and Google Scholar was conducted from inception through April 2025 to identify clinical trials investigating dietary weight-loss or calorie-restriction interventions in adults with overweight or obesity that reported data regarding circulating BDNF outcomes. Eligible studies were clinical trials with interventions lasting ≥4 weeks to investigate circulating BDNF concentrations before and after dietary interventions that were conducted in adults (≥18 years old) with baseline overweight or obesity. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Risk of bias was assessed using the Cochrane risk-of-bias tool. Data on study design, participant characteristics, dietary interventions, and BDNF outcomes were extracted and synthesized qualitatively. A summary table of the included studies was generated. Fifteen clinical studies (n = 862 total participants) met inclusion criteria (11 randomized trials and 4 single-arm trials). Diet modalities included continuous calorie restriction (typically 20%-30% caloric deficit), intermittent fasting (eg, alternate-day fasting, time-restricted eating), ketogenic diets (KDs), Mediterranean-type diets, and other weight-loss diets. Duration of interventions ranged from 6 to 26 weeks. Responses to BDNF varied by intervention. In adults with overweight/obesity, weight-loss dietary interventions demonstrated heterogeneous effects on circulating BDNF. We categorized the included studies into 3 groups based on the effects of dietary weight loss on BDNF: increases, no significant change, or decreases. Approximately half of the studies showed no significant effect, while a few interventions showed a decrease. Intermittent fasting regimens and certain dietary patterns (eg, the Mediterranean-DASH [Dietary Approaches to Stop Hypertension] [MIND] diet, and the KD) tend to elevate BDNF levels, whereas continuous calorie restriction often shows no change, and very rapid weight loss may paradoxically reduce BDNF in some cases. These findings suggest that diet-induced weight loss can influence neurotrophic status, potentially modulating brain health. However, results are inconsistent across studies. Overall, interventions involving intermittent calorie restriction, MIND, and/or KD, more frequently reported BDNF increases, whereas continuous calorie restriction produced mixed results. Show less

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that, through the activation of its full length receptor, TrkB-FL, plays a pivotal role in neuroprotection, namely against neuronal toxicity mediated by amyloid-β peptide (Aβ). In astrocytes, the increase of calcium (Ca Show less