Table 1 NRG 1- 4 selected functions [1, 4, 8,9,10,11,12,13,14,15,16,17,18,19,20]
From: Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer
NRG type | Normal function | Disease implications: cancer | Disease implications: neurologic/psychiatric and other disorders | References |
|---|---|---|---|---|
NRG1 | -Influences normal neuronal function such as the development and maintenance of neurons and glia in the nervous system -Expressed in brain, heart, liver, kidneys, spinal cord, ovaries, and skin -Promotes myelination in glia-neuron interactions -Focused in the axonal areas of the neuron -Impacts enteric nervous system development -Influences expression of acetylcholine receptors in synaptic vesicles during neuromuscular junction formation -Affects growth of skeletal muscle cells -Impacts lobuloalveolar budding/milk production in the breast, differentiation of breast cancer cells, myocardium development | -Fusions related to malignancies includes NRG1-CD74, NRG1-SDC4, NRG1-CDH1 (refer to Fig. 1B and Tables 2 and 3) -NRG1 fusions enhance the function of NRG1 | -Alterations in NRG1/ERBB4 signaling possibly related to amyotrophic lateral sclerosis (e.g., ERBB4 I712M), schizophrenia and cognitive disorders such as Alzheimer’s disease -May be involved in Parkinson’s disease -Linked to cardiac development and disease -ERBB4/HER4 mutations in neurologic disease including amyotrophic lateral sclerosis are loss of function | |
NRG2 Also referred to as neural-and-thymus derived activator for ERBB kinases (NTAK) | -Expressed in the brain (mainly in the olfactory bulb, cerebellum, and hippocampus) and thymus -NRG-2, secreted from astrocytes, bound to ErbB3 on neurons and promoted neuronal survival -Regulates voltage gates ion channels and neurotransmitter receptors of neighboring neurons (i.e., astrocyte functions) | -CD74-NRG2alpha fusion in lung cancer has been described | -May be involved in schizophrenia | |
NRG3 | -Neuronal development, proliferation, differentiation, and plasticity -NRG-3 has a key function in promoting early mammary morphogenesis | -NRG-3 is involved in breast cancer | -May be involved in Alzheimer’s disease and schizophrenia -NRG3 mutations, especially those that result in overexpression, may cause symptoms synonymous to those seen in attention deficit hyperactive disorder, as well as broader cognition disorders. | |
NRG4 | -An adipocytokine in which proper expression levels can subvert non-alcoholic fatty liver disease -Aids brown adipose tissue in maintaining normal lipid levels within the liver. -Regulates glucose and lipid metabolism. | Â | -Lowered expression may contribute to obesity-related disorders in a pleiotropic manner -NRG-4 expression was decreased in human inflammatory bowel disease samples and mouse models of colitis, suggesting that activation of ErbB4 is altered -May be involved in schizophrenia |