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Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson's disease models.

Communications biology (2021-02-21)
Jack Wuyang Jin, Xuelai Fan, Esther Del Cid-Pellitero, Xing-Xing Liu, Limin Zhou, Chunfang Dai, Ebrima Gibbs, Wenting He, Hongjie Li, Xiaobin Wu, Austin Hill, Blair R Leavitt, Neil Cashman, Lidong Liu, Jie Lu, Thomas M Durcan, Zhifang Dong, Edward A Fon, Yu Tian Wang

Convincing evidence supports the premise that reducing α-synuclein levels may be an effective therapy for Parkinson's disease (PD); however, there has been lack of a clinically applicable α-synuclein reducing therapeutic strategy. This study was undertaken to develop a blood-brain barrier and plasma membrane-permeable α-synuclein knockdown peptide, Tat-βsyn-degron, that may have therapeutic potential. The peptide effectively reduced the level of α-synuclein via proteasomal degradation both in cell cultures and in animals. Tat-βsyn-degron decreased α-synuclein aggregates and microglial activation in an α-synuclein pre-formed fibril model of spreading synucleinopathy in transgenic mice overexpressing human A53T α-synuclein. Moreover, Tat-βsyn-degron reduced α-synuclein levels and significantly decreased the parkinsonian toxin-induced neuronal damage and motor impairment in a mouse toxicity model of PD. These results show the promising efficacy of Tat-βsyn-degron in two different animal models of PD and suggest its potential use as an effective PD therapeutic that directly targets the disease-causing process.

Product Number
Product Description

Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, L-glutamine, sodium pyruvate, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride, powder
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Goat serum
Urethane, ≥99%
Cytotoxicity Detection Kit (LDH), suitable for protein quantification, suitable for cell analysis, detection, sufficient for ≤2,000 tests
MPP+ iodide, ≥98% (HPLC), powder