Ascorbic acid inhibits PMP22 expression by reducing cAMP levels

Kaya, Ferdinand; Belin, Sophie; Bourgeois, P.; Micaleff, Joelle; Blin, Olivier; Fontés, Michel

doi:10.1016/j.nmd.2006.12.008

Cited by 68 publications

(61 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1c, the largest modification occurs with regard to Mbp in COA, indicating that astrocyte proximity induces a faster maturation (Ceruti et al 2011) than db-cAMP treatment. However, the larger modification with regard to Pmp22 in the case of db-cAMP treatment confirms the reported relationship between cAMP level and expression of Pmp22 (Kaya et al 2007). Schwann cell specific Pmp22 is particularly interesting since although the gene is transcribed into mRNA in oligodendrocytes (Dugas et al 2006;Nielsen et al 2006) it is not translated into protein because of the interaction between miR-9 and the 3 0 UTR of Pmp22 (Lau et al 2008).…”

Section: Discussionsupporting

confidence: 81%

Plasticity of the myelination genomic fabric

2012

View full text Add to dashboard Cite

This study aimed to quantify the influence of the astrocyte proximity on myelination genomic fabric (MYE) of oligodendrocytes, defined as the most interconnected and stably expressed gene web responsible for myelination. Such quantitation is important to evaluate whether astrocyte signaling may contribute to demyelination when impaired and remyelination when properly restored. For this, we compared changes in the gene expression profiles of immortalized precursor oligodendrocytes (Oli-neu), stimulated to differentiate by the proximity of nontouching astrocytes or treatment with db-cAMP. In a previous paper, we reported that the astrocyte proximity upregulated or turned-on a large number of myelination genes and substantially enriched the Ca(2+)-signaling and cytokine receptor regulatory networks of MYE in Oli-neu cells. Here, we introduce the "transcriptomic distance" to evaluate fabric remodeling and "pair-wise relevance" to identify the most influential gene pairs. Together with the prominence gene analysis used to select and rank the fabric genes, these novel analytical tools provide a comprehensively quantitative view of the physio/pathological transformations of the transcriptomic programs of myelinating cells. Applied to our data, the analyses revealed not only that the astrocyte neighborhood is a substantially more powerful regulator of myelination than the differentiating treatment but also the molecular mechanisms of the two differentiating paradigms are different. By inducing a profound remodeling of MYE and regulatory transcriptomic networks, the astrocyte-oligodendrocyte intercommunication may be considered as a major player in both pathophysiology and therapy of neurodegenerative diseases related to myelination.

show abstract

Section: Discussionsupporting

confidence: 81%

Plasticity of the myelination genomic fabric

2012

View full text Add to dashboard Cite

show abstract

“…They strongly suggest that AA promotes Schwann cell myelin formation. Furthermore, in vitro and animal studies showed that AA improves the clinical and pathological phenotype of a mouse model of Chercot-Marie-tooth disease 1A (CMT1A) (Kaya et al, 2007;Passage et al, 2004), which led to various clinical trials examining AA administration in CMT1A. However, none of these trials showed a signifi cant benefi t of AA in the treatment of CMT1A patients (Burns et al, 2009;Micallef et al, 2009;Verhamme et al, 2009).…”

Section: Vitamin C In the Central Nervous Systemmentioning

confidence: 99%

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Nualart¹,

Salazar²,

Oyarce³

et al. 2012

Biol. Res.

View full text Add to dashboard Cite

Stem cells are considered a valuable cellular resource for tissue replacement therapies in most brain disorders. Stem cells have the ability to self-replicate and diff erentiate into numerous cell types, including neurons, oligodendrocytes and astrocytes. As a result, stem cells have been considered the "holy grail" of modern medical neuroscience. Despite their tremendous therapeutic potential, little is known about the mechanisms that regulate their diff erentiation. In this review, we analyze stem cells in embryonic and adult brains, and illustrate the diff erentiation pathways that give origin to most brain cells. We also evaluate the emergent role of the well known anti-oxidant, vitamin C, in stem cell diff erentiation. We believe that a complete understanding of all molecular players, including vitamin C, in stem cell diff erentiation will positively impact on the use of stem cell transplantation for neurodegenerative diseases.

show abstract

“…Some clinical parameters even improved during treatment, suggesting partial reversion of the phenotype. The mechanism underlying downregulation of PMP22 by AA is still not completely known; it is possible that it acts by influencing cAMP levels in Schwann cells (SC) [19]. & This observation led to the initiation of randomized controlled trials (RCTs) to test AA efficacy for the human disease.…”

Section: Gene Dosagementioning

confidence: 99%

Inherited Neuropathies

Schenone

Nobbio

Bragadin

et al. 2011

Curr Treat Options Neurol

View full text Add to dashboard Cite

Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific therapies are not yet available. In clinical practice, rehabilitative strategies remain the most helpful therapeutic approach to these patients. There is still a lack of consensus on the best way to rehabilitate patients affected by CMT. Based on our personal experience and on a review of the literature, we first recommend the prescription of ankle-foot orthoses (AFO) for patients affected by CMT; the choice of which patient, which AFO, and when to apply it depends on the individual condition of each patient and on the experience of the physician/therapist. Second, adaptive equipment (eg, button hook, long-handled shoehorn, elastic shoe laces) is available to compensate for hand deformities, sensory loss, and weakness. Third, moderate to intense strength training and aerobic exercise are well tolerated by patients affected by CMT; further studies are needed to establish whether these approaches are effective in improving their motor function and strength. There is not enough evidence to recommend muscle stretching exercises or proprioceptive kinesiotherapy, although in our experience both approaches may be helpful in selected CMT patients to prevent tendon retractions, muscle tightening, and loss of strength, and to improve balance. There is growing knowledge of the underlying genetic defects and molecular pathophysiology in CMT. To date, only a few clinical trials in CMT patients have been performed. A neurotrophic factor, neurotrophin 3, was used in a small sample of CMT1A patients with promising results, but it has not been tested in a larger cohort and there is currently no reason to suggest this therapy for CMT1A neuropathy. Based on positive results in an animal model of CMT1A, three trials with ascorbic acid (AA) were completed in a large number of patients with this neuropathy, with results that were negative overall. Therefore, it is not possible to recommend the use of AA in CMT1A patients at this time, but the results of a larger Italian-UK study and an American trial with higher doses of AA are still awaited. It is important to remember that a superimposed inflammatory/disimmune process may complicate the course of the neuropathy; in this case, severe worsening (especially motor) in a matter of weeks or months is a "red flag" that should suggest immunosuppressive or immunomodulatory treatment such as steroids, intravenous immunoglobulin, or plasma exchange. In fact, steroid-sensitive cases of HMSN were described many years ago, well before the genetic diagnosis was available. Symptomatic treatment to reduce neuropathic and nociceptive pain, both of which have been reported in patients affected by CMT, should be prescribed according to ...

show abstract

Ascorbic acid inhibits PMP22 expression by reducing cAMP levels

Cited by 68 publications

References 27 publications

Plasticity of the myelination genomic fabric

Plasticity of the myelination genomic fabric

Typical and atypical stem cells in the brain, vitamin C effect and neuropathology

Inherited Neuropathies

Contact Info

Product

Resources

About