Tat-βsyn-degron (trifluoroacetate salt)

Tat-βsyn-degron is an α-synuclein knockdown peptide.¹ It is composed of the HIV-1 Tat plasma membrane transduction domain, the α-synuclein binding domain βsyn which corresponds to amino acids 36-45 of β-synuclein, and the proteasomal targeting domain degron. Tat-βsyn-degron binds to recombinant α-synuclein in a peptide-protein binding assay and reduces α-synuclein levels in primary rat cortical neuron cultures, an effect that can be prevented by the proteasomal inhibitor MG132. In vivo, Tat-βsyn-degron (40 mg/kg) reduces brain α-synuclein levels in M38 transgenic mice that overexpress human A53T mutant α-synuclein. It also reduces phosphorylated α-synuclein levels in the substantia nigra and the pons, as well as neuroinflammation in a mouse model of spreading synucleinopat induced by α-synuclein preformed fibrils. Tat-βsyn-degron (6 µmol/kg, i.p.) protects against dopaminergic neuron loss and rescues motor deficits in a mouse model of MPTP-induced Parkinson’s disease.