Glial Growth Factor Rescues Schwann Cells of Mechanoreceptors from Denervation-Induced Apoptosis

Kopp, Diane M.; Trachtenberg, Joshua T.; Thompson, Wesley J.

doi:10.1523/jneurosci.17-17-06697.1997

Cited by 94 publications

(69 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the postnatal period in rodents, denervation induces apoptosis of both terminal SCs associated with neuromuscular junctions and SCs associated with the mechanoreceptors, Golgi tendon organs and Pacinian corpuscles. Treatment with recombinant NRG1 type II can improve survival of these populations of SCs [99,100]. Similarly, postnatal SCs in the sciatic nerve were protected from axotomy-induced apoptosis on treatment with recombinant NRG1 type II [101].…”

Section: Potential Mechanisms Of Action Of Nrg1 Signaling In Periphermentioning

confidence: 94%

The Role of Neuregulin-1 In the Response To Nerve Injury

Fricker

Bennett

2011

Future Neurol.

View full text Add to dashboard Cite

Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development. In adulthood, NRG1 is dispensable for the maintenance of the myelin sheath; however, this factor is required for both axon regeneration and remyelination following nerve injury. The outcome of NRG1 signaling depends on interactions with other pathways within Schwann cells such as Notch, integrin and cAMP signaling. In certain circumstances, this signaling pathway may be maladaptive; for instance, direct binding of Mycobacterium leprae onto erbB2 receptors produces excessive activation and can actually promote demyelination. Attempts to modulate this pathway in order to promote nerve repair will therefore need to give consideration to the exact isoform used, as well as how it is processed and the context in which it is presented to the Schwann cell. Keywordsneuregulin-1; neuropathy; peripheral nerve injury; regeneration; remyelination; repair; Schwann cell Peripheral nerve injury causes significant morbidity and reduced quality of life as a consequence of weakness, sensory loss and neuropathic pain. In total, 6% of the elderly population suffer from peripheral neuropathy [1], which can be caused by metabolic diseases such as diabetes, inherited genetic disorders such as Charcot-Marie-Tooth disease, infectious and inflammatory disorders including Guillan-Barré syndrome and traumatic injury to the nerve (which alone effects up to 300,000 people in Europe per year [1,2]). In contrast to the CNS, peripheral nerves have a significant regenerative capacity [3]; however, in patients, regeneration and the clinical outcome are often poor. Axons regenerate at a rate of approximately 1 mm per day, depending on the site of the lesion. There may be a delay of months if not years before the target zone is re-innervated, and by this time, the target organ and supporting cells may have irreversibly changed, becoming much less receptive to reinnervation. The current approaches to peripheral nerve repair following nerve transection are either to surgically suture the nerve or to bridge the gap between the two cut ends. Financial & competing interests disclosureThe authors have no other rel evant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Europe PMC Funders Group NRGs & the PNSNRGs Neuregulins are a family of growth factors en...

show abstract

Section: Potential Mechanisms Of Action Of Nrg1 Signaling In Periphermentioning

confidence: 94%

The Role of Neuregulin-1 In the Response To Nerve Injury

Fricker

Bennett

2011

Future Neurol.

View full text Add to dashboard Cite

show abstract

“…Wild-type mice (n ϭ 4) were analyzed with heterozygous mice (n ϭ 4) and DINE-deficient mice (n ϭ 4). Immunohistochemistry was performed essentially as described previously (Kopp et al, 1997), with minor alternations. The sections were rinsed three times in PBS, permeabilized by immersion in absolute MeOH for 6 min at Ϫ30°C (except for the use of anti-choline acetyltransferase and ␣-bungarotoxin), rinsed in PBS for 30 min, and blocked for 30 min in a solution (diluent) consisting of 0.3% Triton X-100, 0.2% bovine serum albumin (BSA), and 0.1% sodium azide in PBS.…”

Section: Methodsmentioning

confidence: 99%

Damage-Induced Neuronal Endopeptidase Is Critical for Presynaptic Formation of Neuromuscular Junctions

Nagata

Kiryu‐Seo²,

Maeda³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

Damage-induced neuronal endopeptidase (DINE) is a metalloprotease belonging to the neprilysin family. Expression of DINE mRNA is observed predominantly in subsets of neurons in the CNS and peripheral nervous system during embryonic development, as well as after axonal injury. However, the physiological function of DINE and its substrate remain unknown. We generated DINE-deficient mice to examine the physiological role of DINE. Shortly after birth, these mice died of respiratory failure resulting from a dysfunction of the diaphragm, which showed severe atrophy. As DINE was abundantly expressed in motor neurons and there was atrophy of the diaphragm, we analyzed the interaction between motor nerves and skeletal muscles in the DINE-deficient mice. Although there were no obvious deficiencies in numbers of motor neurons in the spinal cord or in the nerve trajectories from the spinal cord to the skeletal muscle in DINE-deficient mice, detailed histochemical analysis demonstrated a significant decrease of nerve terminal arborization in the diaphragm from embryonic day 12.5. In accordance with the decrease of final branching, the diaphragms from DINE-deficient mice exhibited only a few neuromuscular junctions. Similar changes in nerve terminal morphology were also apparent in other skeletal muscles, including the latissimus dorsi and the intercostal muscles. These data suggest that DINE is a crucial molecule in distal axonal arborization into muscle to establish neuromuscular junctions.

show abstract

“…These two molecules, acetylcholine receptor-inducing activity or ARIA Falls et al, 1993), and glial growth factor or GGF (Marchionni et al, 1993), activate phosphorylation of p185 HER-2/neu and promote mitogenesis in cells of the peripheral nervous system. More recent data shows that GGF rescues peripheral nervous system cells from various apoptosis-induced conditions (Kopp et al, 1997;Raabe et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Akita²,

et al. 1999

View full text Add to dashboard Cite

The heregulins are a family of ligands with ability to induce phosphorylation of the p185 HER-2/neu receptor. Various investigators have reported a variety of responses of mouse and human breast and ovarian cells to this family of ligands including growth stimulation, growth inhibition, apoptosis and induction of di erentiation in cells expressing the HER-2/neu receptor. Some of the disparity in the literature has been attributed to variations in the cell lines studied, ligand dose applied, methodologies utilized or model system evaluated (i.e. in vitro or in vivo). To evaluate the e ects of heregulin on normal and malignant human breast and ovarian epithelial cells expressing known levels of the HER-2/ neu receptor, this report presents the use of several di erent assays, performed both in vitro and in vivo, in vitro proliferation assays, direct cell counts, clonogenicity under anchorage-dependent and anchorage-independent conditions, as well as the in vivo e ects of heregulin on human cells growing in nude mice to address heregulin activity. Using a total of ®ve di erent biologic assays in nine di erent cell lines, across two di erent epithelia and over a one log heregulin dose range, we obtained results that clearly indicate a growth-stimulatory role for this ligand in human breast and ovarian epithelial cells. We ®nd no evidence that heregulin has any growth-inhibitory e ects in human epithelial cells. We also quantitated the amount of each member of the type I receptor tyrosine kinase family (RTK I, i.e. HER-1, HER-2, HER-3 and HER-4) in the cell lines employed and correlated this to their respective heregulin responses. These data demonstrate that HER-2/neu overexpression itself a ects the expression of other RTK I members and that cells expressing the highest levels of HER-2/neu have the greatest response to HRG.

show abstract

Glial Growth Factor Rescues Schwann Cells of Mechanoreceptors from Denervation-Induced Apoptosis

Cited by 94 publications

References 49 publications

The Role of Neuregulin-1 In the Response To Nerve Injury

The Role of Neuregulin-1 In the Response To Nerve Injury

Damage-Induced Neuronal Endopeptidase Is Critical for Presynaptic Formation of Neuromuscular Junctions

Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells

Contact Info

Product

Resources

About