What is the BDNF pathway?
BDNF signalling is the neurotrophin pathway through which TrkB receptor activation and downstream myokine crosstalk are studied in muscle-brain axis research.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin, a secreted growth factor of the neurotrophin family, and the pathway named for it is the signalling cascade initiated when BDNF binds its high-affinity receptor, tropomyosin receptor kinase B (TrkB). In the muscle-brain axis literature, BDNF is handled as one of a set of myokines and exerkines — alongside irisin/FNDC5, interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), cathepsin B, and growth differentiation factor-15 (GDF-15) — through which skeletal muscle is proposed to communicate with the ageing brain [1]. The evidence block supplied for this page does not give a sequence, molecular formula, or molecular weight for BDNF, so none is stated here.
The work centres on the neurotrophin/TrkB receptor family and on the irisin-BDNF axis, a pathway described in the ageing literature as a modulator of neuroplasticity and neurotrophic signalling [2].
Research Studies
BDNF and the muscle-brain axis in sarcopenia-associated cognitive decline
A narrative review synthesising mechanistic and translational evidence reported that sarcopenia and cognitive decline frequently co-occur in older adults and that the two conditions appear to share a common biological substrate centred on the muscle-brain axis [1]. In that framing, skeletal muscle signals to the ageing brain through myokines and exerkines, and BDNF is listed among them. The same review reported that progressive sarcopenia disrupts this signalling in a way proposed to accelerate cognitive impairment [1]. The population concerned is older adults; the review is a synthesis of mechanistic and translational work rather than a primary trial.
Irisin-BDNF signalling and neuroplasticity in ageing
A second narrative review reported that age-related cognitive decline is closely associated with diminished neuroplasticity and disrupted neurotrophic signalling, and that exercise is a potent modulator of the irisin-BDNF axis [2]. That review described the axis as having emerging relevance to healthy ageing, neuroprotection, and the prevention of neurodegenerative diseases in older adults [2]. The population named is older adults.
Exercise as the modulator studied across both reviews
Both sources converge on physical activity as the experimental variable applied to the pathway. One review treats exercise as a potent modulator of the irisin-BDNF axis [2]; the other situates BDNF within a broader exerkine set whose release is tied to muscle activity and whose disruption tracks with sarcopenia [1]. Neither source, as summarised in the evidence block, reports a dose, a training protocol, or a measured effect size.
Myokine and exerkine members compared
The evidence block names six molecules in the muscle-brain signalling set. Their roles are not interchangeable, and the table below records only what the source states.
| Molecule | Class as described | Reported role in the source |
|---|---|---|
| Irisin / FNDC5 | Myokine / exerkine | Component of the irisin-BDNF axis modulated by exercise [2]; listed in muscle-brain signalling [1] |
| BDNF | Neurotrophin | Listed among myokines/exerkines mediating muscle-brain communication [1]; downstream node of the irisin-BDNF axis [2] |
| IL-6 | Myokine / exerkine | Listed among muscle-brain signalling molecules [1] |
| IGF-1 | Myokine / exerkine | Listed among muscle-brain signalling molecules [1] |
| Cathepsin B | Myokine / exerkine | Listed among muscle-brain signalling molecules [1] |
| GDF-15 | Myokine / exerkine | Listed among muscle-brain signalling molecules [1] |
Model systems and the limits of the evidence
Both sources are narrative reviews rather than primary experimental reports. One describes itself as synthesising mechanistic and translational evidence and reports database searches in PubMed, Scopus and further databases [1]. The other is likewise a narrative review [2]. Neither evidence entry specifies whether the underlying findings were obtained in animal models, in vitro preparations, or human participants, so this page does not assign them to a model system. Where a claim is not supported by the evidence block, it is omitted.
Population named in the cognitive-decline findings
The population named in both sources is older adults. One review reports that sarcopenia and cognitive decline frequently co-occur in that group [1]; the other reports that age-related cognitive decline in older adults is closely associated with diminished neuroplasticity and disrupted neurotrophic signalling [2]. No paediatric, clinical, or non-ageing population is named in the evidence block.
What the pathway description does and does not establish
The evidence supports describing BDNF as a neurotrophin within a muscle-brain signalling set [1] and as a node in an exercise-modulated irisin-BDNF axis [2]. It does not supply receptor-binding constants, downstream second-messenger detail, tissue-specific expression values, or quantitative effect sizes. Those details are therefore absent from this page rather than inferred.
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Sources
- [1] Myokines as molecular mediators of the muscle-brain axis: Mechanisms linking sarcopenia to cognitive decline and implications for preventive strategies in ageing — A narrative review. https://pubmed.ncbi.nlm.nih.gov/42520997/
- [2] Exercise-induced irisin-BDNF signaling in aging: implications for cognitive decline, sarcopenia, and neurodegeneration. A narrative review. https://pubmed.ncbi.nlm.nih.gov/42644357/