A Fruit Fly Model for Amyotrophic Lateral Sclerosis

Bing Zhang, Ph.D.
University of Oklahoma
NIEHS Grant R21ES014441

A multi-university research team has developed a new laboratory model for studying the motor neuron disease amyotrophic lateral sclerosis (ALS). The researchers at the University of Oklahoma and the University of Pennsylvania created a transgenic fruit fly that is able to express human superoxide dismutase, an antioxidant enzyme that has been implicated in the hereditary form of ALS.

ALS is a progressive and fatal neurodegenerative disease of the motor nervous system. It is characterized by the loss of muscle function caused by dysfunction and death of motor neurons throughout the body. Ten to fifteen percent of ALS cases are considered to be of genetic origin. About one-fifth of hereditary ALS cases are linked to mutations in the gene encoding for superoxide dismutase. Uncovering how mutations in the enzyme lead to the dysfunction and death of motor neurons could illuminate how ALS develops and progresses in patients with both sporadic and hereditary forms of the disease.

In experiments using the new model, these researchers found that expression of the enzyme in the flies induced neurological damage along with accumulation of the enzyme in motor neurons accompanied by a stress response in the surrounding glial cells. This work suggests that superoxide dismutase can cause cell-autonomous damage to motor neurons. It also highlights the usefulness of the fruit fly model for studying ALS.

Citation: Watson MR, Lagow RD, Xu K, Zhang B, Bonini NM. A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1. J Biol Chem. 2008 Sep 5;283(36):24972-81.