Abstract

Since its description by Charcot more than 130 years ago, the mechanism underlying the characteristic selective degeneration and death of motor neurons in amyotrophic lateral sclerosis has remained a mystery. Modern genetics has now identified mutations in two genes — SOD1 and ALS2 — as primary causes of the disease, and has implicated others as potential contributors. Insights into these abnormalities, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.

Author affiliations

1. Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
2. Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21288, USA.

Correspondence to: Don W. Cleveland¹ Email: dcleveland@ucsd.edu