Enhanced axonal neuregulin-1 type-III signaling ameliorates neurophysiology and hypomyelination in a Charcot–Marie–Tooth type 1B mouse model

Scapin, Cristina; Ferri, Cinzia; Pettinato, Emanuela; Zambroni, Desirée; Bianchi, Francesca; Carro, Ubaldo Del; Belin, Sophie; Caruso, Donatella; Mitro, Nico; Pellegatta, Marta; Taveggia, Carla; Schwab, Markus H.; Nave, Klaus Armin; Feltri, M. Laura; Wrabetz, Lawrence; D’Antonio, Maurizio

doi:10.1093/hmg/ddy411

Cited by 31 publications

(38 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PMP2 has have high binding affinity to fatty acids and cholesterol [137,138] and is proposed to participate in fatty acid transport and fatty acid metabolism [133,139,140]. Interestingly, several PMP2 mutations were shown to cause a demyelinating form of Charcot-Marie-Tooth disease [141][142][143]; and upregulation of axonal neuregulin signaling causes an increase in PMP2 expression [144,145].…”

Section: Fatty Acid Uptakementioning

confidence: 99%

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

Self Cite

244

152

View full text Add to dashboard Cite

Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

show abstract

Section: Fatty Acid Uptakementioning

confidence: 99%

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Poitelon

Kopec

Belin

2020

Cells

Self Cite

244

152

View full text Add to dashboard Cite

show abstract

“…Niaspan enhances TACE and ameliorates the neuropathy in a mouse model of CMT4B1 with myelin outfoldings by reducing the hypermyelination [111]. Stimulating Nrg1 type III by suppressing TACE improves neuropathy in a mouse model of CMT1B [112]. Thus, regulation of Nrg1 TIII is a potential candidate for a general therapeutic approach for CMT.…”

Section: Other Therapeutic Avenuesmentioning

confidence: 99%

Charcot-Marie-Tooth: From Molecules to Therapy

Morena

Gupta

Hoyle

2019

IJMS

138

105

View full text Add to dashboard Cite

Charcot-Marie-Tooth (CMT) is the most prevalent category of inherited neuropathy. The most common inheritance pattern is autosomal dominant, though there also are X-linked and autosomal recessive subtypes. In addition to a variety of inheritance patterns, there are a myriad of genes associated with CMT, reflecting the heterogeneity of this disorder. Next generation sequencing (NGS) has expanded and simplified the diagnostic yield of genes/molecules underlying and/or associated with CMT, which is of paramount importance in providing a substrate for current and future targeted disease-modifying treatment options. Considerable research attention for disease-modifying therapy has been geared towards the most commonly encountered genetic mutations (PMP22, GJB1, MPZ, and MFN2). In this review, we highlight the clinical background, molecular understanding, and therapeutic investigations of these CMT subtypes, while also discussing therapeutic research pertinent to the remaining less common CMT subtypes.

show abstract

“…Interestingly, administration of exogenous NRG1 type III and NRG1 type I promotes neurite outgrowth and nerve regeneration (Mahanthappa et al, 1996; Cai et al, 2004). Moreover, modulation of NRG1 activity in animal models of CMT1A (Fledrich et al, 2014), CMT1B (Scapin et al, 2018) and Congenital Hypomyelinating Neuropathy (Belin et al, 2018), can ameliorate the peripheral hypomyelination observed in these diseases, prevent axonal loss and promote nerve functional recovery, the latter all features observed also after nerve injury. Nonetheless, it has also been recently reported that NRG1 is already highly expressed in nerves of CMT1A pre-clinical models, thus indicating that delivery of exogenous NRG1 should be carefully evaluated (Fornasari et al, 2018).…”

Section: Neuregulin-1mentioning

confidence: 99%

The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1

Pellegatta

Taveggia

2019

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

After damage, axons in the peripheral nervous system (PNS) regenerate and regrow following a process termed Wallerian degeneration, but the regenerative process is often incomplete and usually the system does not reach full recovery. Key steps to the creation of a permissive environment for axonal regrowth are the trans-differentiation of Schwann cells and the remodeling of the extracellular matrix (ECM). In this review article, we will discuss how proteases and secretases promote effective regeneration and remyelination. We will detail how they control neuregulin-1 (NRG-1) activity at the post-translational level, as the concerted action of alpha, beta and gamma secretases cooperates to balance activating and inhibitory signals necessary for physiological myelination and remyelination. In addition, we will discuss the role of other proteases in nerve repair, among which A Disintegrin And Metalloproteinases (ADAMs) and gamma-secretases substrates. Moreover, we will present how matrix metalloproteinases (MMPs) and proteases of the blood coagulation cascade participate in forming newly synthetized myelin and in regulating axonal regeneration. Overall, we will highlight how a deeper comprehension of secretases and proteases mechanism of action in Wallerian degeneration might be useful to develop new therapies with the potential of readily and efficiently improve the regenerative process.

show abstract

Enhanced axonal neuregulin-1 type-III signaling ameliorates neurophysiology and hypomyelination in a Charcot–Marie–Tooth type 1B mouse model

Cited by 31 publications

References 66 publications

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Charcot-Marie-Tooth: From Molecules to Therapy

The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1

Contact Info

Product

Resources

About