ALS2

The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. This protein is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.

Alsin appears to have many functions, only a few of which are known. Alsin turns on (activates) multiple proteins called GTPases that convert a molecule called GTP into another molecule called GDP. GTPases play important roles in cell division, the process by which cells mature to carry out specific functions (differentiation), and the self-destruction of cells (apoptosis). Alsin is also thought to play a role in cell membrane organization and the transport of molecules from the cell membrane to the interior of the cell (endocytosis). Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.

amyotrophic lateral sclerosis - caused by mutations in the ALS2 gene

At least eight mutations in the ALS2 gene have been found to cause amyotrophic lateral sclerosis (ALS), a condition characterized by progressive movement problems and muscle wasting caused by motor neuron death. ALS2 gene mutations are often associated with the juvenile form of ALS, which develops in a person's teens or twenties. Most of these mutations delete single DNA building blocks (nucleotides) in the ALS2 gene, which alters the instructions for producing alsin. As a result of ALS2 gene mutations, alsin does not function correctly or does not function at all.

It is unclear how the loss of functional alsin protein causes ALS. A reduction in alsin function may disrupt the activation of GTPases and prevent the necessary cell functions that they facilitate. Additionally, a lack of functional alsin may impair the movement of essential molecules into cells or alter the development of axons and dendrites. Researchers suggest that the long axons of motor neurons may be particularly sensitive to altered development. It is likely that a combination of these deficits in function eventually cause motor neurons to die, leading to the signs and symptoms of ALS.

infantile-onset ascending hereditary spastic paralysis - caused by mutations in the ALS2 gene

Researchers have identified several ALS2 gene mutations that cause infantile-onset ascending hereditary spastic paralysis, a disorder characterized by progressive weakness and stiffness of muscles in the arms, legs, and face that begins within the first 2 years of life. The mutations that cause this condition change or delete one or more nucleotides, which alters the instructions for producing alsin. As a result, alsin is unstable and is broken down rapidly by the cell.

It is unclear how the loss of alsin protein causes infantile-onset ascending hereditary spastic paralysis. Loss of alsin may disrupt the movement of essential molecules within cells or alter the development of axons and dendrites. Long axons are thought to be particularly sensitive to altered development. The loss of functional alsin leads to a decline in motor neuron function causing these nerve cells to die, leading to the signs and symptoms of infantile-onset ascending hereditary spastic paralysis.

juvenile primary lateral sclerosis - caused by mutations in the ALS2 gene

Researchers have identified three mutations in the ALS2 gene that cause juvenile primary lateral sclerosis, which is characterized by progressive weakness and stiffness of muscles in the arms, legs, and face that typically begins in childhood. Two of the mutations that cause this disorder delete nucleotides, and one mutation replaces one nucleotide with an incorrect nucleotide. These mutations alter the instructions for producing alsin. As a result, alsin is unstable and is broken down rapidly by the cell, or it is disabled and cannot function properly.

It is unclear how the loss of functional alsin protein causes juvenile primary lateral sclerosis. Loss of alsin may result in a disruption of the movement of molecules within cells or impair the development of axons and dendrites. Researchers suggest that motor neurons and their long axons may be particularly vulnerable to changes in cell development. As a result, motor neuron function declines and eventually these nerve cells die, leading to the signs and symptoms of juvenile primary lateral sclerosis.