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Cited by 3Nerve injury and regenerationPain Mechanisms and TreatmentsHereditary Neurological Disorders

The role of neuritin 1 in synaptic plasticity and sensory nerve function: Integrator of neurotrophic, metabolic and injury signals

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Agrawal, Jyoti, Escola, Mar Vives, Jones, Simon W., Chapman, Victoria, Dajas‐Bailador, Federico·2026·European Journal of Neuroscience
DOI 10.1111/ejn.70493PMC PMC13070893
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Abstract

Neuritin 1 (NRN1) has emerged as a multifaceted regulator of synaptic plasticity, neuronal excitability and structural remodelling. This review synthesises knowledge of NRN1 function across the central and peripheral nervous systems, with a focus on its roles in sensory neurones and neuronal repair following injury. We discuss evidence that NRN1 interacts with classical neurotrophic pathways, including brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF), while engaging distinct cellular mechanisms that span activity‐dependent trafficking, modulation of calcium and potassium channel function and regulated local axonal mRNA translation. Accumulating data indicate that NRN1 contributes to injury‐induced plasticity and functional recovery through both cell‐autonomous neuronal mechanisms and non‐cell‐autonomous signalling involving glial and stromal cells. In long‐projecting sensory axons, regulated transport and local translation of Nrn1 mRNA position NRN1 as a spatially restricted effector of axonal growth, excitability and regeneration. Dysregulation of NRN1 expression and signalling has been implicated in pathological contexts including neurodegeneration, diabetic peripheral neuropathy and inflammatory pain, where restoration of NRN1 activity promotes axonal integrity, Schwann cell survival and neurotrophic support. Beyond neurons, NRN1 also modulates inflammatory and angiogenic pathways, including VEGF and CXCR4 signalling, linking neuronal plasticity to broader tissue and immune responses. Together, these findings support a model in which NRN1 acts as a molecular integrator of neurotrophic, metabolic and injury‐associated signals, coordinating plasticity while also presenting potential routes to maladaptive sensitisation. We highlight key mechanistic and translational challenges that must be addressed to harness NRN1 biology therapeutically aimed at enhancing neuronal repair while limiting persistent sensory dysfunction.

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  • 5xFAD Cass4-/- inhibitory neurons exhibited downregulation of genes and pathways involved in neuronal circuitry.

    “Moreover, we observed a downregulation of genes and pathways involved in neuronal circuitry such as Sv2b , Vav3 , Arhgap24 , Asap2 , Elmo1 , and Nrn1 in 5xFAD Cass4 -/-mice relative to 5xFAD littermate controls (Agrawal et al., 2026; Chan et al., 2020; Cowan et al., 2005; Falace et al., 2024; Hale et al., 2011; Kim et al., 2011; Li et al., 2018; Miyamoto et al., 2020; Pugh et al., 2026; Sauzeau et”

    From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Agrawal et al., 2026

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Sorted by citations

Authors
Agrawal, J., Escola, M. V., Jones, S. W., Chapman, V., & Dajas‐Bailador, F.
Affiliations
  • University of Nottingham (GB)
  • National Institute for Health and Care Research (GB)
Corresponding author
  • Chapman, Victoria
  • Dajas‐Bailador, Federico
ORCID
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2026-04
Volume
63
Issue
7
Pages
e70493-e70493
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
DOI
10.1111/ejn.70493
PMC
PMC13070893
OpenAlex
W7153797740
Cited by
3
References
1
Citations by year
2026: 3
FWCI
2.71
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
  • University of Birmingham Research Portal (University of Birmingham) (publishedVersion, cc-by)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
Funders
  • Versus Arthritis (20777, 23292)
  • Arthritis Research UK
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
synaptic plasticity, sensory neurons, axon regeneration, brain-derived neurotrophic factor, nerve growth factor, calcium channel modulation, potassium channel regulation, Schwann cells, diabetic peripheral neuropathy, inflammatory pain, neurodegeneration, VEGF signaling, angiogenesis
MeSH terms
Animals, Humans, Nerve Regeneration, Neuronal Plasticity, Neuropeptides, Sensory Receptor Cells, Signal Transduction, GPI-Linked Proteins

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