Page 30 - Q. Neuroscience

[Q. Neuroscience-17]

Supplement Of Parkin In Pathogenic Neurons Reduces

Aggregated α-Synuclein And Suppresses Parkinson's Disease-

Associated Phenotypes By Ubiquitin Proteasome System

Sangsun Yoon¹, Yukdong Jung¹, Yunseo Hwang¹, Dongjae Min¹, Jongseok Lee¹, Jaehwa Lee¹, Hyunwoo Kang¹,

Joohyun Pi¹, Youngsil Choi¹, Daewoong Jo¹

¹Cellivery R&D Institute, Cellivery Therapeutics Inc, Seoul 03929, Korea

Parkinson's disease (PD) is a neurodegenerative disorder, which is pathologically characterized by dopaminergic

neuronal loss and formation of Lewy bodies (LB) in various brain regions including substantia nigra (SN) and striatum.
Approximately, 90% of LB consists of Ser-129 phosphorylated α-Synuclein as an aggregated form. Improved cell-

permeable Parkin (iCP-Parkin), as a PD-therapeutic agent capable of delivery to the brain, has been developing by
fusing Parkin with a sequence-optimized hydrophobic cell-penetrating peptide, namely advanced macromolecule

transduction domain (aMTD). As a result, iCP-Parkin is able to be delivered into the brain by penetrating blood-
brain barrier and has a therapeutic effect in adeno-associated virus (AAV)-α-Synuclein-induced PD model

(stereotaxic injection in SN), and iCP-Parkin (30 mg/kg, 3 times/week for 4 weeks) significantly recovered motor
function, as assessed by behavior tests (rota-rod: 90%; pole: 72%). Moreover, the expression of tyrosine hydroxylase

and α-Synuclein were significantly regulated (+63% & -68%, respectively). These results suggest that iCP-Parkin has
cytoprotective effect in dopaminergic neuronal cells with a reduction of aggregated α-Synuclein, offering a novel

potential therapeutic opportunity in PD treatment.