Motor neuron diseases
- Lesion
Motor neuron diseases kill the nerve cells that move muscles; ALS takes both upper and lower motor neurons and causes progressive paralysis.
What it is
Motor neuron diseases are degenerations of the neurons that control skeletal muscle. Amyotrophic lateral sclerosis destroys upper motor neurons in the motor cortex and lower motor neurons in the brainstem and anterior horns, sparing sensation, and is usually fatal within a few years from respiratory failure. Most cases are sporadic; familial ones involve C9orf72, SOD1, TARDBP or FUS. Kennedy disease is an X-linked polyglutamine disorder of lower motor neurons, and spinal muscular atrophy is a recessive disease of infancy and childhood caused by SMN1 loss.
Step by step
- Genetic or sporadic triggers disturb RNA processing or protein handling (TDP-43, SOD1).
- Motor neurons, large and long, accumulate damage; glutamate toxicity and glia add injury.
- Upper motor neurons die and the lateral corticospinal tracts degenerate.
- Lower motor neurons die; muscles lose innervation, twitch and waste.
- Breathing muscles weaken, causing respiratory failure.
Motor neuron diseases compared
| Disease | Neurons | Genetics | Clue |
|---|---|---|---|
| ALS | Upper and lower | Mostly sporadic; C9orf72, SOD1, TARDBP, FUS | TDP-43 inclusions; often with FTD |
| Kennedy disease | Lower (and dorsal root ganglia) | X-linked, CAG in androgen receptor | Gynecomastia, men only |
| Spinal muscular atrophy | Lower | Autosomal recessive, SMN1 loss | Infant hypotonia, tongue fasciculations |
| Poliomyelitis (acquired) | Lower | Viral | Asymmetric, acute |
Clinical notes
- ALS often begins with asymmetric hand weakness or bulbar symptoms such as dysarthria and dysphagia.
- Gene-directed therapies have changed the outlook of spinal muscular atrophy.
Test yourself
Think of the answer, then tap the question to see it.
Which neurons are lost in ALS?
Both upper motor neurons in the motor cortex and lower motor neurons in the brainstem and spinal anterior horns.
Which gene is deleted in spinal muscular atrophy?
SMN1 (survival motor neuron 1); the number of SMN2 copies modifies severity.
What is the genetic cause of Kennedy disease?
An X-linked CAG repeat expansion in the androgen receptor gene.
Elsewhere in DurgiPedia
- Upper versus lower motor neuron lesions
- Motor cortex and the corticospinal tract
- Upper vs lower motor neuron syndrome
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Amyotrophic lateral sclerosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Spinal muscular atrophy: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.