Amyotrophic Laterial Sclerosis

What is amyotrophic lateral sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that affects nerve cells in the brain and spinal cord. ALS primarily involves the degeneration of motor neurons, which are the nerve cells responsible for controlling voluntary muscle movement.

 

As ALS progresses, the motor neurons gradually deteriorate and eventually die, leading to muscle weakness, muscle atrophy (shrinkage), and loss of motor function. The exact cause of ALS is not fully understood, but it is believed to involve a combination of genetic and environmental factors.

 

What is the relationship between ALS and oxidative stress?

Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants. In ALS, oxidative stress is thought to contribute to the degeneration of motor neurons, which are the nerve cells affected by the disease.

 

Several factors contribute to oxidative stress in ALS:

 

• Mitochondrial Dysfunction: Mitochondria are the cellular organelles responsible for producing energy. In ALS, dysfunction of mitochondria leads to impaired energy production and increased production of ROS. This can contribute to oxidative stress and neuronal damage.

 

• Glutamate Excitotoxicity: Glutamate is a neurotransmitter that plays a role in transmitting signals between nerve cells. In ALS, dysfunction in the regulation of glutamate levels can lead to excessive accumulation of glutamate in the synaptic space, leading to excitotoxicity and neuronal damage. Excitotoxicity is associated with increased ROS production and oxidative stress.

 

• Protein Aggregation: Abnormal protein aggregation is a characteristic feature of ALS, with misfolded proteins such as superoxide dismutase 1 (SOD1) and TAR DNA-binding protein 43 (TDP-43) forming aggregates in affected neurons. Protein aggregates can induce oxidative stress and impair cellular function, contributing to neuronal degeneration.

 

• Inflammation: Neuroinflammation is another hallmark of ALS, involving activation of immune cells in the central nervous system. Inflammatory processes can lead to the production of ROS and oxidative damage to neurons.

 

• Environmental Factors: Exposure to environmental toxins, such as heavy metals or pesticides, can increase oxidative stress and contribute to the development or progression of ALS.

 

Overall, oxidative stress is believed to be a key pathological mechanism in ALS, contributing to motor neuron degeneration, inflammation, and disease progression.