Glia cells in amyotrophic lateral sclerosis: new clues to understanding an old disease?
In classic neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), the pathogenic concept of a cell-autonomous disease of motor neurons has been challenged increasingly in recent years. Macro- and microglial cells have come to the forefront for their role in multistep degenerative processes in ALS and respective disease models. The activation of astroglial and microglial cells occurs early in the pathogenesis of the disease and seems to greatly influence disease onset and promotion. The role of oligodendrocytes and Schwann cells remains elusive. In this review we highlight the impact of nonneuronal cells in ALS pathology. We discuss diverse glial membrane proteins that are necessary to control neuronal activity and neuronal cell survival, and summarize the contribution of these proteins to motor neuron death in ALS. We also describe recently discovered glial mechanisms that promote motor neuron degeneration using state-of-the-art genetic mouse technology. Finally, we provide an outlook on the extent to which these new pathomechanistic insights may offer novel therapeutic approaches.
Neusch
Clemens
C
Department of Neurology, University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany. cneusch@gwdg.de
Bähr
Mathias
M
Schneider-Gold
Christiane
C
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000503:physiopathology*; D005911:Gliosis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D008565:Membrane Proteins