Glial Cells As Therapeutic Targets For Als

Although Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death, recent studies now implicate the non-neuronal environment as a major contributor to motor neuron loss. This body of evidence has been amassed over the past 10-15 years and highlights glial cells as new therapeutic targets for ALS. Glial cells, once thought to be simply the “glue” of the central nervous system (CNS), are now realized to actively participate in neural transmission and serve complex roles in regulation of the CNS environment. Several glial cell types including astrocytes, microglia, and oligodendrocytes exist in the CNS; each serves a distinct function. Astrocytes comprise the majority of the CNS cellular space and act to regulate neurotransmitter concentrations at synapses, provide trophic support for neurons, and maintain metabolic and ionic homeostasis. Astrocytes can participate in the immune response, however, microglia serve as the resident immune cell of the CNS. Microglia are mobile, phagocytic, and constantly screening the CNS for possible infection or injury. Upon activation, microglia can secrete pro-inflammatory cytokines and chemokines to promote the clearance of any infectious agents and recruit other immune cells to the site of injury. Depending on the stimuli, microglia also are known to release neurotrophic growth factors and anti-inflammatory molecules to aid in repair and resolution of neural damage. Oligodendrocytes are the myelinating glia of the CNS which intimately interact with, and provide metabolic support to neurons. Oligodendrocytes are capable of producing myelin sheaths which insulate axons and aid in the conduction of action potentials. Ongoing research strives to define exactly how glial cells affect motor neuron survival in ALS. Furthermore, translation of these studies to the clinical setting begs for novel approaches to treat this new target for ALS.