| First Author | Chakrabarty P | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 9 | Pages | 2247-2264 |
| PubMed ID | 30158114 | Mgi Jnum | J:265838 |
| Mgi Id | MGI:6201859 | Doi | 10.1084/jem.20180484 |
| Citation | Chakrabarty P, et al. (2018) TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer's disease. J Exp Med 215(9):2247-2264 |
| abstractText | There is considerable interest in harnessing innate immunity to treat Alzheimer's disease (AD). Here, we explore whether a decoy receptor strategy using the ectodomain of select TLRs has therapeutic potential in AD. AAV-mediated expression of human TLR5 ectodomain (sTLR5) alone or fused to human IgG4 Fc (sTLR5Fc) results in robust attenuation of amyloid beta (Abeta) accumulation in a mouse model of Alzheimer-type Abeta pathology. sTLR5Fc binds to oligomeric and fibrillar Abeta with high affinity, forms complexes with Abeta, and blocks Abeta toxicity. Oligomeric and fibrillar Abeta modulates flagellin-mediated activation of human TLR5 but does not, by itself, activate TLR5 signaling. Genetic analysis shows that rare protein coding variants in human TLR5 may be associated with a reduced risk of AD. Further, transcriptome analysis shows altered TLR gene expression in human AD. Collectively, our data suggest that TLR5 decoy receptor-based biologics represent a novel and safe Abeta-selective class of biotherapy in AD. |
