Therapeutic Potential of Hepatocyte Growth Factor for Treating Neurological Diseases

This review summarizes recent findings on the therapeutic potential of hepatocyte growth factor (HGF) for a variety of neurological diseases. HGF, originally identified and molecularly cloned as a potent mitogen for hepatocytes, exhibits multiple biological effects, including mitogenic, motogenic, morphogenic, and anti-apoptotic activities in a wide variety of cells by binding to the c-Met/HGF receptor tyrosine kinase (c-Met). HGF is thus potentially a powerful tool as an organotropic factor for protection and regeneration of a variety of organs, and has an ability to exert the multipotent activities under pathophysiological conditions. In the nervous system, HGF and c-Met are expressed in not only developing brain but also adult mature brain, indicating that HGF-c-Met system plays a functional role in the central nervous system. Indeed, many studies have demonstrated that HGF shows neurotrophic activities in the hippocampal, cerebral cortical, midbrain dopaminergic, motor, sensory, sympathetic, parasympathetic, and cerebellar granule neurons in vitro. In in vivo studies, HGF exerted neuroprotective effects by preventing neuronal cell death in animal models of cerebrovascular diseases including ischemic brain injuries and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). These reports suggested that HGF is an effective therapeutic agent for the treatment of various neurological diseases.