Tat-βsyn-degron, an α-synuclein knockdown peptide, integrates three domains: the HIV-1 Tat plasma membrane transduction domain, an α-synuclein binding domain (βsyn) representing amino acids 36-45 of β-synuclein, and a proteasomal targeting domain (degron). It effectively binds to recombinant α-synuclein, demonstrating a significant reduction in α-synuclein levels in primary rat cortical neuron cultures.

Tat-βsyn-degron (40 mg/kg)能够在过表达人类A53T突变体α-synuclein的M38转基因小鼠的大脑中降低α-synuclein水平，并且在黑质和脑桥中降低磷酸化α-synuclein水平，以及在通过α-synuclein预成纤维诱导的扩散性α-synuclein病理模型小鼠中减少神经炎症。此外，Tat-βsyn-degron (6 µmol/kg, i.p.)在MPTP诱导的帕金森病小鼠模型中，保护多巴胺能神经元，缓解运动缺陷。