Schwann cell development, maturation and regeneration: a focus on classic and emerging intracellular signaling pathways

Abstract

The development, maturation and regeneration of Schwann cells (SCs), the main glial cells of the peripheral nervous system, require the coordinate and complementary interaction among several factors, signals and intracellular pathways. These regulatory molecules consist of integrins, neuregulins, growth factors, hormones, neurotransmitters, as well as entire intracellular pathways including protein-kinase A, C, Akt, Erk/MAPK, Hippo, mTOR, etc. For instance, Hippo pathway is overall involved in proliferation, apoptosis, regeneration and organ size control, being crucial in cancer proliferation process. In SCs, Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical challenges. Recently, among factors regulating SCs, also the signaling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) proved relevant for SC fate, participating in the regulation of adhesion, motility, migration and in vitro myelination. In SCs, the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone, thus corroborating the importance of this steroid in the control of SC maturation. In this review, we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental, mature and regenerative states

Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons

“…Besides these structural purposes, SCs cross-interact with neurons, specifically with whole axons, regulating their physiological functions. A plethora of mediators is produced and/or released by SCs, thus regulating the neuron-glial interaction, including neuropeptides, cytokines, growth factors, integrins, neuregulins, neurotransmitters and neuroactive steroids [3][4][5][6][7].…”

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells

“…The overproduction of ROS damages cellular biomolecules, such as proteins, lipids and nucleic acids, and induces apoptosis in multiple types of cells resulting in the induction of DNA damage and apoptosis 5,6. In particular, Schwann cell apoptosis can enhance axonal degeneration, which is an important cause of peripheral neuropathy induction, due to reduced neurotrophic support from Schwann cells 7,8. Therefore, the inhibition of excessive ROS generation is essential for the maintenance of the neural fiber regeneration function of Schwann cells.…”

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/β‐catenin signaling pathway

“…Consistent with the effects of Foxc1 on cellular migration, overexpression of Foxc1 in SCs promoted its migration. As the major glial cells of the peripheral nervous system, SCs form myelin sheaths, and provide support and nutrition to neurons (Castelnovo et al, 2017). Axonal regeneration is frequently accompanied by SC recruitment following peripheral nerve injury (Su et al, 2019).…”