- Article
- Source: Campus Sanofi
- Sep 16, 2025
Mechanism of Smoldering Disease
Smoldering neuroinflammation is driven primarily by disease-associated microglia found in the CNS and contributes to both physical and cognitive disability accumulation1-3
- Microglia are key orchestrators of smoldering neuroinflammation in the CNS, resulting in disability accumulation1,4
- Even in the earliest stages of MS, microglia shift from a homeostatic to a disease-associated state1
Innate immunity predominantly drives smoldering neuroinflammation1
From peripheral triggers to central drivers: the evolving pathophysiology of acute and smoldering neuroinflammation7,8
Microglia are key orchestrators of smoldering neuroinflammation in the CNS resulting in disability accumulation9
Homeostatic microglia play an important role in regulating myelimation and remyelination, synaptic maintenance, blood-brain barrier permeability, and neurogenesis.10
Even in the earliest stages of MS, microglia shift from a homeostatic to a disease-associated state. 11,12
- Microglia-driven smoldering nouroinflammation begins even before the first clinically apparent relapse or acute lession 1,13,14,15
- Iron-laden microglia surround the lesion edge of paramagnetic rim lesions and are associated with increased disability in both RRMS and SPMS16-17
- Microglia are upregulated in SPMS and are thought to play a significant role in driving disability accumulaton16-18
- Microglia-induced synaptic loss has been associated with cognitive loss19-21
Microglia are upregulated in SPMS and are thought to play a significant role in driving disability accumulation.17,22
Iron-laden microglia surround the lesion edge of paramagnetic rim lesions* (PRLs) and are associated with increased disability in both RRMS and SPMS.23
Microglia-induced synaptic loss has been associated with cognitive loss.19-21
For more information about Acute and Smoldering Inflammation, click on this link:
*PRLs are a type of chronic active lesion (CAL).
CNS, central nervous system; EBV, Epstein-Barr virus; HERV, human endogenous retroviruses; MRI, magnetic resonance imaging; MS, multiple sclerosis; UTI, urinary tract infection.
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