Fig. 1.

Different approaches of therapeutic intervention to mitigate alpha-synuclein aggregate toxicity. (1) Reduction in alpha-synuclein expression by gene therapy, e.g., RNA interference, antisense oligonucleotide (ASO). (2) Inhibition of monomeric alpha-synuclein polymerization or dissolving oligomers and fibrils with peptides or small molecules. (3) Target degradation of alpha-synuclein fibrils by proteasome or autophagy/lysosome machineries. (4) Neutralization of extracellular alpha-synuclein fibrils with antibodies/nanobodies. (5) Block putative alpha-synuclein fibril receptor to prevent internalization and spread of pathology. Mechanistic studies of all these pathways may shed light on innovative therapeutic approaches in the future.