Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons in the brain, brainstem and spinal cord, which is characterized by motor dysfunction, muscle dystrophy and progressive paralysis. Both inherited and sporadic forms of ALS share common pathological features, however, the initial trigger of neurodegeneration remains unknown. Motor neurons are uniquely targeted by ubiquitously expressed proteins in ALS but the reason for this selectively vulnerability is unclear. However motor neurons have unique characteristics such as very long axons, large cell bodies and high energetic metabolism, therefore placing high demands on cellular transport processes. Defects in cellular trafficking are now widely reported in ALS, including dysfunction to the molecular motors dynein and kinesin. Abnormalities to dynein in particular are linked to ALS, and defects in dynein-mediated axonal transport processes have been reported as one of the earliest pathologies in transgenic SOD1 mice. Furthermore, dynein is very highly expressed in neurons and neurons are particularly sensitive to dynein dysfunction. Hence, unravelling cellular transport processes mediated by molecular motor proteins may help shed light on motor neuron loss in ALS.
Highlights
Amyotrophic lateral sclerosis (ALS), known as Charcot’s sclerosis or Lou Gehrig’s disease, is the most common form of motor neuron disease
We describe the functions of the molecular motors, including kinesins and dyneins, as well as their putative roles in ALS
Impaired axonal transport of mitochondria has been reported in ALS [64], a recent study demonstrates that impairment of mitochondrial transport in SOD1G93A transgenic mice plays a minimal role in ALS pathology [65]
Summary
Amyotrophic lateral sclerosis (ALS), known as Charcot’s sclerosis or Lou Gehrig’s disease, is the most common form of motor neuron disease. Several proteins are linked to sporadic and familial forms of ALS, notably superoxide dismutase 1 (SOD1) [1], TAR DNA binding protein 43 (TDP-43) [2], and fused in sarcoma (FUS) [3]. Highly differentiated, polarized cells, with extremely long axons, up to 1 metre in length in an adult human. They have high synthetic and energy requirements, which places heavy demands on cellular transport processes [11]. We describe the functions of the molecular motors, including kinesins and dyneins, as well as their putative roles in ALS
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