Dual role of complement in neuronal repair.

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• The complement system, traditionally viewed as part of innate immunity, significantly influences nervous system health and disease.
• Neuronal survival and axon regeneration are critical challenges in acute injuries and neurodegenerative diseases.

Purpose of the Study:

• To review the complex and often contradictory roles of the complement system in neurodegeneration and neural repair.
• To integrate the roles of extracellular complement pathways with the newly identified intracellular complement system (complosome).

Main Methods:

• Literature review synthesizing evidence on complement's dual functions in the nervous system.
• Examination of molecular mechanisms, including complement receptors (C5aR1), inflammasomes (NLRP3), and intracellular pathways (complosome, mTOR).

Main Results:

• Complement activation can be detrimental, promoting neuroinflammation, apoptosis, and autophagy via C5aR1 and NLRP3 inflammasome.
• Complement also plays beneficial roles, such as phagocyte recruitment (C5a) and synaptic remodeling (C3).
• The intracellular 'complosome' links complement to cellular metabolism, survival, and regeneration via the mTOR pathway.

Conclusions:

• The complement system is a sophisticated network, not merely an inflammatory mediator, with crucial roles in both damaging and regenerative processes in the nervous system.
• Targeting complement pathways offers potential for therapies that mitigate neurodegeneration while promoting neural repair.