Axonal Regeneration and Neuroinflammation: Roles for the Translocator Protein 18 kDa
Abstract
After a traumatic injury of the nervous system or in the course of a neurodegenerative disease, the speed of axonal regeneration and the control of the inflammatory response are fundamental parameters of functional recovery. Spontaneous regeneration takes place in the peripheral nervous system, although the process is slow and often incomplete. There is currently no efficient treatment for enhancing axonal regeneration, including elongation speed and functional reinnervation. Ligands of the translocator protein 18 kDa (TSPO) are currently under investigation as therapeutic means for promoting neuroprotection, accelerating axonal regeneration and modulating inflammation. The mechanisms of action of TSPO ligands involve the regulation of mitochondrial activity and the stimulation of steroid biosynthesis. In the peripheral nervous system, TSPO expression is strongly up-regulated after injury, primarily in Schwann cells and macrophages, but also in neurones. Its levels return to low control values when nerve regeneration is completed, strongly supporting an important role in regenerative processes. We have demonstrated a role for the benzoxazine etifoxine in promoting axonal regeneration in the lesioned rat sciatic nerve, either after freeze-injury or complete transection. Etifoxine is already clinically approved for the treatment of anxiety disorders (Stresam(®) , Biocodex, Gentilly, France). Daily treatment with etifoxine resulted in a two-fold acceleration in axonal regenerati…
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TSPO is expressed in almost all CNS cells, including astrocytes, neurons and endothelial cells.
“Although increased TSPO expression has historically been mostly associated with microglial activation, TSPO is now known to be expressed in almost all CNS cells including astrocytes, neurons and endothelial cells [21–27], all of which may also be involved in, or be affected by neuroinflammation [28].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [23]
TSPO is present in immature neurons.
“Studies have demonstrated the presence of TSPO in immature neurons, as well as in differentiating/regenerating neurons [23, 24, 52].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [23]
TSPO is present in differentiating/regenerating neurons.
“Studies have demonstrated the presence of TSPO in immature neurons, as well as in differentiating/regenerating neurons [23, 24, 52].”
From Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease (2023) · cites this paper as [23]
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“Studies have demonstrated the presence of TSPO in immature neurons, as well as in differentiating/regenerating neurons [23, 24, 52].”
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- Authors
- Girard, C., Liu, S., Adams, D., Lacroix, C., Sinéus, M., Boucher, C., Papadopoulos, V., Rupprecht, R., Schumacher, M., & Groyer, G.
- Affiliations
- Inserm (FR)
- Research Institute of the McGill University Health Centre (CA)
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Groyer, G.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2011-12-20
- Volume
- 24
- Issue
- 1
- Pages
- 71-81
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W1680745702
- Cited by
- 75
- References
- 10
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 8 · 2015: 16 · 2014: 4 · 2013: 4
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- translocator protein (TSPO), TSPO ligands, etifoxine, axon regeneration, peripheral nerve injury, sciatic nerve transection, frost damage, neuroinflammation, macrophage activation, Schwann cells, pregnenolone synthesis, steroidogenesis, mitochondrial activity, TNF-α, IL-1β, functional recovery, peripheral neuropathy, neuroprotection
- MeSH terms
- Animals, Axons, Encephalitis, Nerve Regeneration, Receptors, GABA, Recovery of Function, Peripheral Nerve Injuries
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