Glia in amyotrophic lateral sclerosis and spinal cord injury: common therapeutic targets

Abstract

The toolkit for repairing damaged neurons in amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI) is extremely limited. Here, we reviewed the in vitro and in vivo studies and clinical trials on nonneuronal cells in the neurodegenerative processes common to both these conditions. Special focus was directed to microglia and astrocytes, because their activation and proliferation, also known as neuroinflammation, is a key driver of neurodegeneration. Neuroinflammation is a multifaceted process that evolves during the disease course, and can be either beneficial or toxic to neurons. Given the fundamental regulatory functions of glia, pathogenic mechanisms in neuroinflammation represent promising therapeutic targets. We also discussed neuroprotective, immunosuppressive, and stem-cell based approaches applicable to both ALS and SCI.

Figure 1

Amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI) hallmarks. Specific and common features of these neurodegenerative diseases. Asterisk: Wallerian degeneration, a typical dying-forward neurodegenerative process in SCI, has also been reported in ALS, although dying-back hypothesis is now gaining more ground (123); Double asterisk: the massive infiltration of peripheral blood cells is specific for SCI, whereas increased permeability to blood-borne factors is common to both ALS and SCI. BBB/BSCB – blood-brain/blood-spinal cord barrier.