Amyotrophic Lateral Sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder in which premature loss of motor neurons
leads to muscle weakness, atrophy and paralysis. For the past 15 years, investigators have relied on the use of mutations
in SOD1 to model this motor neuron disease, yet, recent advances in the genetics of ALS provide opportunities to develop new
animal models to study disease pathophysiology and to identify new directions for therapeutic development. Investigators have
utilized mutations in genes such as FUS/TLS and TARDBP to develop models of disease in a spectrum of diverse organisms including
yeast, worms, flies, zebrafish and rodents.
Frontotemporal lobar degeneration (FTLD) represents a group of degenerative brain disorders characterized by progressive damage to neurons in the anterior temporal and/or frontal lobes of the brain. Recent genetic advances have demonstrated that mutations in TARDBP, which encodes the trans-active response DNA-binding protein 43 (TDP-43) are also associated with FTLD. The identification of TDP-43 protein pathology in both sporadic ALS and in the most common pathological subtype of FTLD (frontotemporal lobar degeneration with ubquitinated inclusions) further suggests a spectrum of diseases encompassing classic motor neuron disease at one end and FTLD at the other.
The workshop focused on the strategies used to generate ALS and FTLD disease models and the lessons learned from the pathological, biochemical, molecular and behavioral analyses of these model systems. Investigators in the fields of ALS and FTLD participated in the workshop which was sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) and the Amyotrophic Lateral Sclerosis Association (ALSA).
Amelie Gubitz, Ph.D.
National Institute of Neurological Disorders and Stroke
Phone: (301) 496-5680
Last updated December 23, 2013