Immune system alterations in amyotrophic lateral sclerosis

Area of Science:

• Neuroimmunology
• Neurodegenerative diseases

Background:

• The exact cause and pathogenesis of amyotrophic lateral sclerosis (ALS) remain unknown.
• Growing evidence suggests a non-cell autonomous mechanism involving multiple cell types in ALS.
• Immune system alterations are increasingly recognized as integral to ALS pathogenesis.

Purpose of the Study:

• To review evidence supporting the immune system's role in ALS.
• To present a hypothesis on the interplay of immune cells in ALS pathogenesis.
• To guide future research directions in ALS.

Main Methods:

• Literature review of studies on immune system involvement in ALS.
• Analysis of data on immune cell activation and infiltration in ALS.
• Examination of the complement system's role in neurodegeneration.

Main Results:

• The immune system actively participates in ALS pathogenesis.
• Activated microglia, astrocytes, and the complement system contribute to neurodegeneration.
• Peripheral immune cell infiltration correlates with disease progression, though composition is unclear.
• Elevated classical complement pathway markers and C1q from motor neurons observed.
• Activated microglia and astrocytes surround dying motor neurons, increasing with disease progression.

Conclusions:

• The interplay of immune cells, including microglia, astrocytes, and peripheral immune cells, is crucial in ALS.
• The detrimental effects of this immune system collaboration appear to dominate protective aspects.
• Understanding this complex interplay is vital for advancing ALS research and therapeutic strategies.