Role of Interleukin-1 in Prion Disease-Associated Astrocyte Activation

Abstract

Prion-induced chronic neurodegeneration has a substantial inflammatory component, and the activation of glia cells may play an important role in disease development and progression. However, the functional contribution of cytokines to the development of the gliosis in vivo was never systematically studied.

Investigation ofMcp1as a Quantitative Trait Gene for Prion Disease Incubation Time in Mouse

“…Both pro-and anti-inflammatory molecules have been implicated in prion disease incubation time (Schultz et al 2004;Thackray et al 2004;Felton et al 2005) and their results are all consistent with the hypothesis that inflammation may accelerate neuronal loss. However, our results demonstrate that the effects of individual molecules are likely to be prion-strain specific and therefore it may not be possible to extrapolate to human prion diseases where their role remains uncertain.…”

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…In consequence, several studies have focused in the study of the role of glial cells in prion diseases. As mentioned, although neuronal apoptosis is important in prion-associated neural degeneration (Gray et al, 1999), microglial/astroglial recruitment is crucial for the progression of the disease (Baker et al, 2002;Depino et al, 2003;Giese et al, 1998;Giese and Kretzschmar, 2001;Marella and Chabry, 2004;Schultz et al, 2004).…”

Microglia in prion diseases

“…CXCL9 and CXCL10, which recognize and bind to CXCR3, are also increased in prion infection (64,71). After intracerebral inoculation of 139A prion, Cxcr3 -/-mice accumulated more PrP Sc in their brains compared with WT mice, but succumbed to disease with a prolonged incubation time (72).…”

“…While most cytokines (TNF-α, IL-6, TGF-β1, etc.) do not play an important role in prion-induced neurodegeneration in the CNS, knockout of IL-1 receptor 1 (IL-1R1), which is the receptor for IL-1α and IL-1β, led to a modest but statistically significant delay in disease progression (64,65). This may be due to delayed astrogliosis and/or augmented microglial activation that contribute to enhanced phagocytosis of prions in Il1r1 -/-mice.…”