Amyotrophic Lateral Sclerosis (ALS) and Immune Response: Can Inflammation Be a Contributing Factor?

Amyotrophic lateral sclerosis (ALS) is the most common progressive motor neuron disease and represents a primary and devastating neurodegenerative condition. The manifestations of ALS include insidious asymmetric weakness, hyperreflexia, extensor plantar response, increased muscle tone, muscle atrophy, hyporeflexia, muscle cramps, and fasciculations (muscle twitching). Ultimately, involvement of respiratory muscles leads to death. Numerous studies indicate that alterations in immune responses may play a role in the pathogenesis of ALS. Resident astrocytes, microglial cells, and infiltrating T cells in the central nervous system (CNS) have garnered specific attention regarding neuroinflammatory processes associated with ALS. Oxidative stress appears to be a key factor in the onset and progression of the disease in both sporadic ALS (sALS) and familial ALS (fALS). The degeneration of motor neurons activates microglia to release reactive oxygen species (ROS) and pro-inflammatory cytokines. Once established, inflammation and immune changes may either exacerbate or protect against damage. The prevalence of immune-mediated diseases (IMDs) in patients with ALS has been widely reported. One study provides evidence that prior IMDs, particularly those affecting the endocrine and gastrointestinal systems, are associated with an increased risk of developing ALS in women. IL-۱۸ in circulation seems to act as a marker for neuroinflammation, indicating the activation of caspase-۱ and the localized effects of IL-۱β, although it is not considered a useful biomarker for tracking sALS patients. Immune and inflammatory changes in ALS may be primary factors contributing to the disease etiology. Alternatively, neuroinflammation and T cell infiltration may also be secondary responses to tissue damage occurring in ALS, as observed in other forms of nervous system injury. Currently, there is compelling evidence suggesting that abnormal immune alterations are not only significant features of ALS but may also serve as risk factors for its onset. Anti-inflammatory treatments, including IL-۱β inhibition, could be beneficial for ALS patients. As of now, ALS remains untreatable. Various factors may explain the failure of anti-inflammatory modulators and other medications to slow disease progression in ALS patients.

کلیدواژه ها:

Amyotrophic Lateral Sclerosis ، Astrocyte ، Oxidative stress ، immune-mediated diseases