Which peptides are studied in relation to the BDNF pathway?
A research-supply overview of the peptides examined in BDNF-pathway studies, including irisin/FNDC5, BDNF itself, IGF-1, IL-6, cathepsin B and GDF-15, with notes on which findings are animal-only or in vitro.
The peptide most frequently studied in relation to the brain-derived neurotrophic factor (BDNF) pathway is irisin, the cleaved product of the fibronectin type III domain-containing protein 5 (FNDC5) gene. Irisin is a myokine — a peptide secreted by skeletal muscle — and in the research literature it is treated as an upstream regulator of BDNF expression rather than as a neurotrophin itself. BDNF is the mature peptide ligand of the tropomyosin receptor kinase B (TrkB) receptor, and the work described here centres on the irisin–BDNF axis and on the other muscle-derived peptides that feed into it.
Beyond irisin, the peptides and peptide hormones that appear alongside BDNF in this literature include BDNF itself, insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), cathepsin B and growth differentiation factor-15 (GDF-15). These are grouped as myokines and exerkines — factors released by contracting skeletal muscle and other tissues during exercise — and the shared hypothesis is that they mediate communication between muscle and brain [1].
Research Studies
Irisin/FNDC5 and BDNF expression in the ageing brain
Irisin is the best-characterised peptide in this area. Reviews of the irisin–BDNF axis describe it as a molecular pathway with emerging relevance to healthy ageing, neuroprotection and the prevention of neurodegenerative disease in older adults [2]. The proposed mechanism is that exercise raises circulating irisin, which in turn is associated with increased BDNF and downstream neuroplasticity signalling. Much of the mechanistic detail in this literature derives from animal and in vitro work rather than from controlled human studies.
BDNF and TrkB signalling in the muscle-brain axis
BDNF is included in the myokine and exerkine set in its own right, not only as a downstream target. A narrative review of the muscle-brain axis lists BDNF alongside irisin/FNDC5, IL-6, IGF-1, cathepsin B and GDF-15 as factors through which skeletal muscle communicates with the ageing brain [1]. The receptor family at the centre of this work is TrkB, the high-affinity receptor for mature BDNF.
Irisin and BDNF in sarcopenia-associated cognitive decline
Sarcopenia and cognitive decline frequently co-occur in older adults, and the muscle-brain axis review argues that the two conditions share a common biological substrate [1]. In that framing, progressive loss of muscle mass disrupts myokine signalling — including irisin and BDNF — and this disruption is proposed to accelerate cognitive impairment. The evidence synthesised is mechanistic and translational; the review is narrative rather than a meta-analysis of trial data [1].
IGF-1 and BDNF in the same myokine panel
IGF-1 appears in the muscle-brain axis literature as one of the exerkines examined alongside BDNF [1]. It is treated as part of a panel of muscle-derived factors rather than as an isolated BDNF regulator, and the review does not report a single causal chain from IGF-1 to BDNF.
IL-6 and BDNF: exercise-associated cytokine signalling
Interleukin-6 is listed among the myokines in the muscle-brain axis review [1]. Its inclusion reflects the broader observation that contracting muscle releases cytokines that can act on the central nervous system, but the review presents IL-6 as one component of a multi-factor signalling environment rather than as a direct BDNF modulator.
Cathepsin B and BDNF in exercise-linked neuroplasticity
Cathepsin B is another muscle-derived factor named in the same myokine and exerkine set [1]. As with IL-6 and IGF-1, it is discussed as part of the panel of factors through which muscle activity is proposed to influence brain function, not as a standalone BDNF-pathway peptide.
GDF-15 and BDNF in ageing muscle-brain signalling
Growth differentiation factor-15 completes the list of myokines and exerkines in the muscle-brain axis review [1]. The review's organising claim is that these factors collectively link sarcopenia to cognitive decline, with BDNF among the neurotrophic components of that signalling network.
Comparison of peptides studied in the BDNF pathway
| Peptide | Class / origin | Reported relationship to BDNF pathway | Evidence type in cited reviews |
|---|---|---|---|
| Irisin / FNDC5 | Myokine, cleaved from FNDC5 | Upstream regulator of BDNF in the irisin–BDNF axis | Narrative review; mechanistic and translational [1][2] |
| BDNF | Neurotrophin, TrkB ligand | Central neurotrophic factor of the pathway | Narrative review [1] |
| IGF-1 | Myokine / growth factor | Panel member in muscle-brain signalling | Narrative review [1] |
| IL-6 | Myokine / cytokine | Panel member in muscle-brain signalling | Narrative review [1] |
| Cathepsin B | Muscle-derived protease | Panel member in muscle-brain signalling | Narrative review [1] |
| GDF-15 | Myokine / TGF-β family | Panel member in muscle-brain signalling | Narrative review [1] |
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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/