Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and...

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglial and astrocytic reactivity is a hallmark of amyotrophic lateral sclerosis (ALS).
• These glial cells are increasingly recognized for their critical roles in ALS disease progression.
• Glial cells exhibit diverse functional states influenced by context, including disease.

Purpose of the Study:

• To review recent advances in understanding microglial and astrocytic states and nomenclature in ALS.
• To highlight key discoveries linking glial cells to ALS pathogenesis.
• To discuss novel therapeutic strategies targeting glial cells in ALS clinical trials.

Main Methods:

• Literature review of recent advancements in ALS research.
• Analysis of findings from rodent and cell models of ALS.
• Examination of ongoing clinical trials for ALS therapeutics targeting glial cells.

Main Results:

• Glial cells (microglia and astrocytes) demonstrate both neuroprotective and neurotoxic functions in ALS models.
• Distinct functional states of glial cells are crucial in disease pathogenesis.
• Several novel therapeutic candidates targeting glial cells are progressing through clinical trials.

Conclusions:

• Microglia and astrocytes are central players in ALS pathogenesis, with context-dependent functions.
• Understanding glial cell states is vital for developing effective ALS therapies.
• Targeting glial cells represents a promising therapeutic avenue for amyotrophic lateral sclerosis.