%0 Journal Article %A Omid Tavassoly %A Takashi Sato %A Iman Tavassoly %T Inhibition of Brain EGFR Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries %D 2020 %R 10.1124/mol.120.119909 %J Molecular Pharmacology %P mol.120.119909 %X Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathological and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal cord injuries (SCI). Despite successful therapeutics effects of EGFR inhibition in these pathological conditions, there is still no report of proof-of-concept studies in well-characterized animal models using recently developed Blood-Brain-Barrier (BBB) penetrating EGFR inhibitors which is due to previous conflicting reports concerning the level of EGFR or activated EGFR in normal and pathological conditions which caused target engagement a concern in any future EGFR inhibition therapy. In this review, the level of EGFR expression and activation in developing CNS compared to adult CNS will be explained as well as how neuronal injury or pathological conditions especially inflammation and amyloid fibrils induce reactive astrocytes leading to increase in the expression and activation of EGFR and finally neurodegeneration. Furthermore, in this review, we will discuss two main molecular mechanisms that can be proposed as neuroprotective effects of EGFR inhibition in these pathological conditions. We will also review the recent advances in the development of BBB- penetrating EGFR inhibitors in cancer therapy, which may eventually be repositioned for NDDs and SCI therapy in the future.SIGNIFICANCE STATEMENT Based on lessons from applications of EGFR inhibitor in oncology, it is concluded that EGFR inhibitors can be beneficial in treatment of neurodegenerative diseases and spinal cord injuries. They carry their therapeutic potentials through induction of autophagy and attenuation of reactive astrocytes. %U https://molpharm.aspetjournals.org/content/molpharm/early/2020/04/26/mol.120.119909.full.pdf