**1. Introduction**

454 Amyotrophic Lateral Sclerosis

Wright LS, Li J, Caldwell MA, Wallace K, Johnson JA & Svendsen CN. (2003) Gene

Xu L, Ryugo DK, Pongstaporn T, Johe K & Koliatsos VE. (2009) Human neural stem cell

Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, Takahashi

Yan J, Xu L, Welsh AM, Chen D, Hazel T, Johe K & Koliatsos VE. (2006) Combined

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J,

Zoccolella S, Santamato A & Lamberti P. (2009) Current and emerging treatments for

transgenic mice. *Stem Cells*. 2006 Aug; Volume 24(8); Pages 1976-85.

*Neurochem.* 2003 Jul; Volume 86(1): Pages 179-95.

514(4); Pages 297-309.

Volume 11(3); Pages 251-3.

Volume 318(5858); Pages 1917-20.

Epub 2009 Nov 16.

expression in human neural stem cells: effects of leukemia inhibitory factor. *J* 

grafts in the spinal cord of SOD1 transgenic rats: differentiation and structural integration into the segmental motor circuitry. *J Comp Neurol*. 2009 Jun 1; Volume

R, Misawa H & Cleveland DW. (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. *Nat Neurosci*. 2008 Mar;

immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis

Jonsdottir GA, Ruotti V, Stewart R, Slukvin II & Thomson JA. (2007) Induced pluripotent stem cell lines derived from human somatic cells. *Science*. 2007 Dec 21;

amyotrophic lateral sclerosis. *Neuropsychiatr Dis Treat.* 2009 May Pages 577-95.

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.
