Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• preclinical characterization of lead compounds that may ultimately provide novel drugs to treat patients suffering from ALS. Keywords: amyotrophic lateral sclerosis (ALS); copper/zinc (Cu-Zn) superoxide dismutase 1 (SOD1); glutamate toxicity; neurodegeneration; oxidative stress; Introduction Amyotrophic

• characterized in ALS, including, but not limited to glutamate toxicity, protein misfolding and aggregation, endoplasmic reticulum (ER) stress, loss of trophic factors, oxidative stress, inflammation, disrupted protein trafficking, and mitochondrial dysfunction [5]. Therapeutic development has been based around

• effective these models are in therapeutic discovery. Reduction in glutamate toxicity Riluzole (1), the only currently approved treatment for attenuating disease progression in ALS patients, both inhibits the release of glutamate and noncompetitively inhibits postsynaptic NMDA and AMPA receptors [6]. However