| First Author | Dutta D | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 5382 |
| PubMed ID | 34508096 | Mgi Jnum | J:314207 |
| Mgi Id | MGI:6764252 | Doi | 10.1038/s41467-021-25767-1 |
| Citation | Dutta D, et al. (2021) Selective targeting of the TLR2/MyD88/NF-kappaB pathway reduces alpha-synuclein spreading in vitro and in vivo. Nat Commun 12(1):5382 |
| abstractText | Pathways to control the spreading of alpha-synuclein (alpha-syn) and associated neuropathology in Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are unclear. Here, we show that preformed alpha-syn fibrils (PFF) increase the association between TLR2 and MyD88, resulting in microglial activation. The TLR2-interaction domain of MyD88 (wtTIDM) peptide-mediated selective inhibition of TLR2 reduces PFF-induced microglial inflammation in vitro. In PFF-seeded A53T mice, the nasal administration of the wtTIDM peptide, NEMO-binding domain (wtNBD) peptide, or genetic deletion of TLR2 reduces glial inflammation, decreases alpha-syn spreading, and protects dopaminergic neurons by inhibiting NF-kappaB. In summary, alpha-syn spreading depends on the TLR2/MyD88/NF-kappaB pathway and it can be reduced by nasal delivery of wtTIDM and wtNBD peptides. |
