Mutant α-synuclein propagates via the lymphatic system of the brain in the monomeric state

• DOI: 10.1016/j.celrep.2023.112962
• Publication Date: 2023-08-16T14:27:38Z
• Authors: Kyota Fujita; Hidenori Homma; Meihua Jin; Yuki Yoshioka; Xiaocen Jin; Yuko Saito; Hikari Tanaka; Hitoshi Okazawa
• Keywords: Lymphatic System; Mice; QH301-705.5; CP: Neuroscience; Blotting, Western; alpha-Synuclein; Animals; Brain; Parkinson Disease; Mutant Proteins; Biology (General)

Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the vivo pattern and aggregation state of mutant α-synuclein by injecting adeno-associated viral (AAV)-α-synuclein-A53T-EGFP into mouse olfactory cortex. Comparison states various brain regions at multiple time points after injection using western blot analyses shows that monomeric mutant/misfolded propagates to remote 2 weeks propagated proteins aggregate situ being incorporated neurons. Moreover, Alexa 488-labeled α-synuclein-A53T confirms weeks. Super-resolution microscopy both propagate via lymphatic system, penetrate perineuronal nets, reach surface Electron monomer forms fibrils characteristic Parkinson's disease its incorporation These findings suggest mode different from aggregate-dependent propagation.