Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder whose pathological hallmark is the loss of motor neurons of the corticospinal pathway. While ALS is a heterogeneous disorder, numerous mechanistic themes, including impaired RNA processing, protein aggregation, intracellular stress, and gliosis, are common to many forms of ALS. In this review we discuss how these mechanisms contribute to selective motor neuron vulnerability and degeneration. In doing so, we synthesize knowledge gained from genetic, molecular, and biochemical studies of human ALS patients and ALS model systems. We conclude with a systematic discussion of the interplay of disease mechanisms and opportunities these mechanisms afford for therapeutic intervention.
|Original language||English (US)|
|Title of host publication||Molecular and Cellular Therapies for Motor Neuron Diseases|
|Number of pages||39|
|State||Published - Jan 19 2017|
- Motor neuron
- Protein aggregation
- RNA binding protein