Hepatocyte Growth Factor (HGF): Neurotrophic Functions and Therapeutic Implications for Neuronal Injury/Diseases

Hiroshi      Funakoshi; Toshikazu      Nakamura

Abstract

Hepatocyte growth factor (HGF), which was originally identified and molecularly cloned as a potent mitogen for primary hepatocytes, exhibits multiple biological effects, such as mitogenic, motogenic, morphogenic, and antiapoptotic activities, in the liver and other organs throughout the body by binding to the c-Met/HGF receptor tyrosine kinase (c-Met). In addition to hepatotrophic activities, HGF and c-Met are expressed in both developing and adult mature brains and nerves, and plays functional roles in the central as well as peripheral nervous systems. A large number of studies have accumulated evidence showing that HGF is a multipotent growth factor that functions as a novel neurotrophic factor for a variety of neurons, including the hippocampal, cerebral cortical, midbrain dopaminergic, motor, sensory, sympathetic, parasympathetic and cerebellar granule neurons in vitro. In vivo, HGF exerts neuroprotective effects in the animal model of cerebrovascular diseases, spinal cord injury, neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), and neuroimmune diseases, preventing neuronal cell death and functioning on glial, vascular and immune cells. The multiple activities of HGF, in addition to highly potent neurotrophic activities, suggest that HGF is a potential therapeutic agent for the treatment of various diseases of the nervous system. Furthermore, the anxiolytic activity of HGF and an association of c-met with autism, as well as neurorecognition and schizophrenia, have been reported, suggesting a role for HGF in emotional and psychiatric status. This review describes the role of HGF in the nervous systems during development and focuses on the therapeutic potential of HGF for a variety of neurological, neuroimmunological and psychiatric diseases among adults.

Keywords: HGF, c-Met, neurotrophic, amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), autophagy, Hepatocyte growth factor, neurons, astrocyte, oligodendrocyte, microglia, neurogenesis, angiogenesis, spinal cord injury, multiple sclerosis, brain ischemia, Alzheimer's disease, Parkinson's disease, dendritic cells, T cells, neuropathy, Schizophrenia, Autism, anxiety, learning and memory, mutation, brain