We recently observed that amyloid fibrillar structures induced pro-inflammatory cytokine secretion through specific recognition of aggregated structure by TLRs and NLRs (4). While fibrillar lysozyme (characterized by parallel β sheet structure) is recognized by TLR2 and NLRP3, amorphous aggregates (characterized by anti-parallel β sheet structure) did not cause any immune responses. This suggested that aggregates organised in cross-β structures are recognized by immune receptors as a danger signal and that somehow the innate system is sensitive to a specific cross beta structure whatever the sequence. This observation has been confirmed for amyloid β(2) and synuclein fibrils. This observation can be related to recent work (1) demonstrating that receptors TLR2 and NLRP3 are involved in the development of Alzheimer disease even if the molecular mechanism remains unknown. These data will be discussed as well as the role of apolipoproteins (ApoE4,ApoE3) and calcium in the stabilisation of specific aggregates (fibrils,oligomers).
1-Heneka MT-Nature 2012-493,674-78
2-Cerf, E Biochem J. (2009) 421, 415-23
3-Cerf, E FASEB J (2011) 25, 1585-95
4-Gustot, A Cell Mol. Life Sci. (2013) 70, 2999-3012