Disease Mechanisms


ALS, or Amyotrophic Lateral Sclerosis, is a neurodegenerative disease that targets motor neurons in the brain and spinal cord. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs), responsible for transmitting signals from the brain to muscles throughout the body. The progressive degeneration of these neurons leads to their death, resulting in the loss of the brain's ability to control muscle movement.

Motor neurons are unique for their exceptional length, extending fibers (axons) up to a meter to reach distant parts of the body. Their metabolic demands are accordingly high. Glial cells, such as astrocytes and oligodendrocytes, which support motor neurons in the central nervous system, also play a role in ALS.

Research has identified various disease processes in ALS:

Axon Structure and Dynamics: ALS may involve disruptions in the transport of materials along motor neuron axons, impacting cell health and message flow.

Cell Death: Apoptosis and Necrosis: Apoptosis, a programmed cell death process, is crucial to nervous system development. ALS researchers aim to understand and potentially halt this process. Necrosis, a different type of cell death resulting from injury or infection, can lead to inflammation and immune activation.

Mitochondria: Mitochondria, responsible for energy production, are vital for sustaining the energy demands of motor neurons in ALS. There is growing evidence suggesting that activities within or stemming from the mitochondria may play a significant role in the disease. Intriguingly, alterations in the mitochondria can be identified before observable physical changes, such as hind limb weakness in mice. Furthermore, mitochondria exhibit early damage in the progression of ALS, prompting researchers to conduct intensive studies on this cellular component.

Glutamate: Prolonged exposure to glutamate, a neurotransmitter, can be toxic to nerve cells. ALS is associated with changes in glutamate concentration. Substantial evidence indicates that glutamate plays a detrimental role in ALS, and researchers are actively exploring ways to alter this impact. Investigative efforts include the examination of gene therapy approaches aimed at supplying glutamate transporters to ALS-affected cells. Additionally, various strategies for controlling glutamate in ALS are currently being actively investigated. Notably, riluzole, the first approved specific treatment for ALS, is a drug that regulates glutamate.

Inflammation: Neuroinflammation, part of the immune system's response, accompanies motor neuron death in ALS. Inflammatory events may provide targets for drug action, focusing on immune system messengers and reducing inflammation caused by overactive glial cells.

Understanding ALS disease mechanisms is crucial for defining its causes and developing therapeutic targets. Given the heterogeneity of ALS, multiple treatment approaches targeting various disease processes may be beneficial for individuals living with the disease. Researchers worldwide are actively working to uncover these mechanisms and direct their efforts towards effective treatments.

Learn More

National Institute of Neurological Disorders and Stroke (NINDS): NINDS is a part of the National Institutes of Health (NIH) and provides comprehensive information on neurological disorders, including ALS. It includes information on research, clinical trials, and publications.

PubMed is a database of biomedical literature and scientific articles. You can search for specific research papers and reviews related to ALS and biomarkers to access in-depth information.