Neuregulin-1/ErbB network: An emerging modulator of nervous system injury and repair

Abstract

Neuregulin-1 (Nrg-1) is a member of the Neuregulin family of growth factors with essential roles in the developing and adult nervous system. Six different types of Nrg-1 (Nrg-1 type I-VI) and over 30 isoforms have been discovered; however, their specific roles are not fully determined. Nrg-1 signals through a complex network of protein-tyrosine kinase receptors, ErbB2, ErbB3, ErbB4 and multiple intracellular pathways. Genetic and pharmacological studies of Nrg-1 and ErbB receptors have identified a critical role for Nrg-1/ErbB network in neurodevelopment including neuronal migration, neural differentiation, myelination as well as formation of synapses and neuromuscular junctions. Nrg-1 signaling is best known for its characterized role in development and repair of the peripheral nervous system (PNS) due to its essential role in Schwann cell development, survival and myelination. However, our knowledge of the impact of Nrg-1/ErbB on the central nervous system (CNS) has emerged in recent years. Ongoing efforts have uncovered a multi-faceted role for Nrg-1 in regulating CNS injury and repair processes. In this review, we provide a timely overview of the most recent updates on Nrg-1 signaling and its role in nervous system injury and diseases. We will specifically highlight the emerging role of Nrg-1 in modulating the glial and immune responses and its capacity to foster neuroprotection and remyelination in CNS injury. Nrg-1/ErbB network is a key regulatory pathway in the developing nervous system; therefore, unraveling its role in neuropathology and repair can aid in development of new therapeutic approaches for nervous system injuries and associated disorders.

Keywords: CNS injury and repair; ErbB signaling; Myelination and myelin repair; Neuregulin-1; Neuroinflammation; PNS injury.