Fig. 1

Molecular mechanisms in the pathology of amyotrophic lateral sclerosis. a Schematic representation of healthy spinal cord motor neuron. b Schematic representation of ALS affected spinal cord motor neuron: 1) Astrocytes are not able to support neuronal functions and impaired glutamate clearance leads to neuronal excitotoxicity; 2) Defects in protein degradation pathways and disturbances in RNA processing result in protein aggregate formation, RNA toxicity and mitochondrial dysfunction; 3) The secretion of pro-inflammatory cytokines by predominant M1 activated microglia contributes to the development of an inflammatory milieu; 4) Failure of axonal architecture and transport functions, together with the alteration of the physiological role of oligodendrocytes results in 5) synaptic failure, denervation and finally, muscle atrophy