Identification of a Peripherin Dimer: Changes During Axonal Development and Regeneration of the Rat Sciatic Nerve

Chadan, S.; Moya, Kenneth L.; Portier, Marie‐Madeleine; Filliatreau, Ghislaine

doi:10.1046/j.1471-4159.1994.62051894.x

Cited by 24 publications

(10 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A). The intermediary filament peripherin is present in all small axons and re-expressed during nerve regeneration (20,21). At 7 days after injury, small degenerated axons with stained granules persisted in the nerves of vehicle-treated animals, although in etifoxinetreated animals a large number of linear peripherinimmunoreactive axons was observed at this stage (Fig.…”

Section: Resultsmentioning

confidence: 94%

Etifoxine improves peripheral nerve regeneration and functional recovery

Girard

Liu

Cadepond

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

136

112

View full text Add to dashboard Cite

Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.inflammation ͉ macrophage ͉ axonal growth ͉ Translocator Protein (18 kDa)

show abstract

Section: Resultsmentioning

confidence: 94%

Etifoxine improves peripheral nerve regeneration and functional recovery

Girard

Liu

Cadepond

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

136

112

View full text Add to dashboard Cite

show abstract

“…This process could therefore sequester peripherin monomers, which would not be available for neurofilament assembly. Thus, if peripherin is involved in axonal regeneration, as previously suggested [25, 26, 61, 67, 92], the presence of CMT2B-causing mutants could be highly detrimental. Another possibility is that RAB7A binding could alter peripherin phosphorylation, either directly or indirectly.…”

Section: Discussionmentioning

confidence: 91%

“…Also, an aggregate-inducing peripherin isoform is upregulated in ALS [94]. Importantly, peripherin is thought to be important in axonal regeneration [25, 26, 61, 67, 92]. Indeed, it has been suggested that the regeneration program is at least in part based on changes to intermediate filament composition and dynamics [87, 92].…”

Section: Introductionmentioning

confidence: 99%

Charcot–Marie–Tooth type 2B disease-causing RAB7A mutant proteins show altered interaction with the neuronal intermediate filament peripherin

et al. 2012

View full text Add to dashboard Cite

Charcot–Marie–Tooth type 2B (CMT2B) is a peripheral ulcero-mutilating neuropathy caused by four missense mutations in the rab7a gene. CMT2B is clinically characterized by prominent sensory loss, distal muscle weakness leading to muscle atrophy, high frequency of foot ulcers and infections that often results in toe amputations. RAB7A is a ubiquitous small GTPase, which controls transport to late endocytic compartments. Although the biochemical and functional properties of disease-causing RAB7A mutant proteins have been investigated, it is not yet clear how the disease originates. To understand how mutations in a ubiquitous protein specifically affect peripheral neurons, we performed a two-hybrid screen using a dorsal root ganglia cDNA library with the purpose of identifying RAB7A interactors specific for these cells. We identified peripherin, an intermediate filament protein expressed primarily in peripheral neurons, as a putative RAB7A interacting protein. The interaction was confirmed by co-immunoprecipitation and pull-down experiments, and established that the interaction is direct using recombinant proteins. Silencing or overexpression of wild type RAB7A changed the soluble/insoluble rate of peripherin indicating that RAB7A is important for peripherin organization and function. In addition, disease-causing RAB7A mutant proteins bind more strongly to peripherin and their expression causes a significant increase in the amount of soluble peripherin. Since peripherin plays a role not only in neurite outgrowth during development but also in axonal regeneration after injury, these data suggest that the altered interaction between disease-causing RAB7A mutants and peripherin could play an important role in CMT2B neuropathy.

show abstract

“…We selected the PRPH-1 gene, which is expressed predominantly in neurons of the PNS and the cranial nerves (Gorham et al 1990;Troy et al 1990a), as the basis for our reporter. PRPH-1 encodes the cytoskeletal protein peripherin and has been shown to respond to injury, increasing its expression in regenerating neurons and downregulating expression after target reconnection (Beaulieu et al 1999b;Chadan et al 1994;Gervasi et al 2003;Troy et al 1990b;Wong and Oblinger 1990). A similar induction during embryonic neural development followed by a postnatal reduction in expression suggests a role for peripherin in maintaining an elongation permissive cytoskeleton in pathfinding axons (Portier et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence

et al. 2008

View full text Add to dashboard Cite

The development of homologous recombination methods for the precise modification of bacterial artificial chromosomes has allowed the introduction of disease causing mutations or fluorescent reporter genes into human loci for functional studies. We have introduced the EGFP gene into the human PRPH-1 locus to create the Peripherin-EGFP (hPRPH1-G) genomic reporter construct. The hPRPH1-G reporter was used to create transgenic mice with an intrinsically fluorescent peripheral nervous system (PNS). During development, hPRPH1-G expression was concomitant with the acquisition of neuronal cell fate and growing axons could be observed in whole embryo mounts. In the adult, sensory neurons were labeled in both the PNS and central nervous system, while motor neurons in the spinal cord had more limited expression. The fusion protein labeled long neuronal processes, highlighting the peripheral circuitry of hPRPH1-G transgenic mice to provide a useful resource for a range of neurobiological applications.

show abstract

Identification of a Peripherin Dimer: Changes During Axonal Development and Regeneration of the Rat Sciatic Nerve

Cited by 24 publications

References 60 publications

Etifoxine improves peripheral nerve regeneration and functional recovery

Etifoxine improves peripheral nerve regeneration and functional recovery

Charcot–Marie–Tooth type 2B disease-causing RAB7A mutant proteins show altered interaction with the neuronal intermediate filament peripherin

Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence

Contact Info

Product

Resources

About