Inflammation and neurodegeneration: the story 'retolled'

Trends Pharmacol Sci. 2012 Oct;33(10):542-51. doi: 10.1016/ Epub 2012 Aug 31.


Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to the pathophysiology of Alzheimer's disease (AD), Parkinson's disease (PD), and related disorders. In this review, the potential role of TLRs in the context of protein aggregation, neuronal degeneration, and genetic risk factors is addressed. In particular, we discuss the evidence derived from experimental models of both AD and PD which suggests that activation of TLRs can have beneficial and detrimental effects on pathological features such as protein aggregation and neuronal death. A deeper understanding of these dichotomous observations could be used for therapeutic benefit.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism*
  • Animals
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / immunology
  • Parkinson Disease / metabolism*
  • Signal Transduction
  • Toll-Like Receptors / metabolism*


  • Toll-Like Receptors