Neuregulin-1 (NRG1) is a member of a subfamily of the epidermal growth factor family and plays an important role in the development of the peripheral nervous system. Through alternative RNA splicing and promoter usage, the NRG1 gene encodes an entire family of more than 15 transmembrane and secreted isoforms. Neuregulin-1 acts as an important regulator in the survival of Schwann cell precursors, Schwann cell proliferation, motility, axon ensheathment and myelination.

Neuregulin-1 can be divided into different according to the N-terminal sequence. Neuregulin-1 Type III, a transmembrane protein, contains an epidermal growth factor-like domain, which alone is adequate to bind and activate ErbB receptor tyrosine kinases. Type III also contains a cysteine-rich domain called “cysteine-rich domain-neuregulins,” that requires a proteolytic cleavage for full activity^1,2.

Knockout studies show that type III is the key isoform required for schwann cell generation. These studies also confirmed that type III isoform is necessary for promoting myelination and to regulate myelin thickness^1,2. 

Several different studies also showed that NRG1 Type III isoform is also an important regulator of cholinergic signaling. Neuregulin-1 Type III regulates the expression of AChR genes and targeting of nAChRs to the neuronal cell surface. This isoform in particular is a critical regulator of presynaptic targeting of α7-containing nAChRs³.