Toll-like receptors (TLRs) are pattern recognition receptors which mediate an inflammatory response upon the detection of specific molecular patterns found on foreign organisms and on endogenous damage-related molecules. These receptors play a major role in the activation of microglia, the innate immune cells of the CNS, and are also expressed in peripheral tissues, including blood mononuclear cells and the gut. It is well established that immune activation, in both the brain and periphery, is a feature of Parkinson's disease as well as other αsynucleinopathies. Aggregated forms of α-synuclein can act as ligands for TLRs (particularly TLR2 and TLR4), and hence these receptors may play a critical role in mediating a detrimental immune response to this protein, as well as other inflammatory signals in Parkinson's and related α-synucleinopathies. In this review, the potential role of TLRs in contributing to the progression of these disorders is discussed. Existing evidence comes predominantly from studies in in vitro and in vivo models, as well as analyses of postmortem human brain tissue Highlights  Misfolded proteins like α-synuclein can act as DAMPs leading to activation of TLRs, a major component of the innate immune system.  TLRs may be a key mediator of neuroinflammatory responses in PD and other αsynucleinopathies.  Targeting TLRs could be an effective therapeutic strategy for reducing neuroinflammation in PD and slowing down the disease progression.

No abstract

No abstract