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- Title
TLR7/8 in the Pathogenesis of Parkinson's Disease †.
- Authors
Campolo, Michela; Filippone, Alessia; Biondo, Carmelo; Mancuso, Giuseppe; Casili, Giovanna; Lanza, Marika; Cuzzocrea, Salvatore; Esposito, Emanuela; Paterniti, Irene
- Abstract
Neuroinflammation and autoimmune mechanisms have a key part in the pathogenesis of Parkinson's disease (PD). Therefore, we evaluated the role of Toll-like receptors (TLRs) as a link between inflammation and autoimmunity in PD. An in vivo model of PD was performed by administration of 1-metil 4-fenil 1,2,3,6-tetraidro-piridina (MPTP) at the dose of 20 mg/kg every 2 h for a total administration of 80/kg, both in single Knock Out (KO) mice for TLR7, TLR 8, and TLR9 and in double KO mice for TLR 7/8-/-. All animals were compared with WT animals used as a control group. All animals were sacrificed after 7 days form the first administration of MPTP. The genetic absence of TLR 7 and 8 modified the PD pathway, increasing the immunoreactivity for TH and DAT compared to PD groups and decreasing microglia and astrocytes activation. Moreover, the deletion of TLR7 and TLR8 significantly reduced T-cell infiltration in the substantia nigra and lymph nodes, suggesting a reduction of T-cell activation. Therefore, our result highlights a possibility that an immunotherapy approach, by using a dual antagonist of TLR 7 and 8, could be considered as a possible target to develop new therapies for Parkinson diseases.
- Subjects
PARKINSON'S disease; SUBSTANTIA nigra; TOLL-like receptors; ANIMAL sacrifice; LYMPH nodes
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 24, p9384
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21249384