Tat-βsyn-degron is an α-synuclein knockdown peptide. Tat-βsyn-degron binds to α-synuclein and reduces α-synuclein levels in primary rat cortical neuron cultures. Tat-βsyn-degron also reduces α-synuclein levels and decreases the parkinsonian toxin-induced neuronal damage and motor impairment in a mouse toxicity model of PD.