Mechanisms for neuronal degeneration in amyotrophic lateral sclerosis and in models of motor neuron death (Review)

Amyotrophic lateral sclerosis (ALS), also referred to as motor neurone dise ase, is a fatal neurological disease that is characterized clinically by pr ogressive muscle weakness, muscle atrophy, and eventual paralysis. The neur opathology of ALS is primary degeneration of upper (motor cortical) and low er (brainstem and spinal) motor neurons. The amyotrophy refers to the neuro genic atrophy of affected muscle groups, and the lateral sclerosis refers t o the hardening of the lateral white matter funiculus in spinal cord (corre sponding to degeneration of the corticospinal tract) found at autopsy. Beca use the mechanisms for the motor neuron degeneration in ALS are not underst ood, this disease has no precisely known causes and no effective treatments . Very recent studies have identified that the degeneration of motor neuron s in ALS is a form of apoptotic cell death that may occur by an abnormal pr ogrammed cell death (PCD) mechanism. In order to treat ALS effectively, we need to understand the mechanisms for motor neuron apoptosis more completel y. Future studies need to further identify the signals for PCD activation i n neurons as they relate to the pathogenesis of ALS and to clarify the mole cular pathways leading to motor neuron apoptosis in animal and cell culture model systems. These studies should lead to a better understanding of moto r neuron death and to the design of new therapeutic experiments critical fo r the future treatment of ALS.