[ALS and neurotrophic factors--HGF as a novel neurotrophic and neuroregenerative factor]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motoneurons and their axons. Although a variety of responsive mutations in superoxide dismutase-1 (SOD1) have been identified in familial cases, more than 90% of ALS cases are sporadic. Therefore, the most beneficial approach to treatment would be to find the common pathological pathway that functions in both familial and sporadic cases during disease onset and progression. Neurotrophic factors may function to prevent the neuronal death and axonal degeneration in ALS that is thought to be the result of aberrant apoptotic cell death. Here we summarize the potential role of classical neurotrophic factors in ALS. We also describe the potential role of hepatocyte growth factor (HGF), a novel neurotrophic factor, in retarding the progression of the disease in a transgenic mouse model expressing SOD1G93A (G93A). In addition to direct neurotrophic activities, HGF functions on the astrocytes of G93A mice to maintain levels of EAAT2, a glial-specific glutamate transporter that might be responsible for the reduction of glutamatergic neurotoxicity of motoneurons. Furthermore, HGF is capable of reducing astrocytosis and microglial accumulation, and thus supports the attention of a glial-dependent mechanism of ALS progression. Although it is a challenging issue, recent advancements in the elucidation of the role of neurotrophic factors in ALS raise the possibility of their use in the treatment of ALS and related disorders.