Page 24 - Q. Neuroscience

[Q. Neuroscience-14]

Replenishing Parkin Protects Dopaminergic Neurons In

Neurotoxin-Induced Parkinson’s Disease Animal Models

Yukdong Jung¹, Yunseo Hwang¹, Dongjae Min¹, Sangsun Yoon¹, Jongseok Lee¹, Jaehwa Lee¹, Hyunwoo Kang¹,
Joohyun Pi¹, Youngsil Choi¹, Daewoong Jo¹

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

Progressive loss of dopaminergic (DA) neurons in the substantia nigra is the neuropathological hallmarks of

Parkinson’s disease (PD). Parkin is an E3 ubiquitin ligase that plays a cytoprotective role by eliminating damaged
mitochondria. To replenish Parkin as a DA neuronal-protector, improved cell-permeable (iCP) Parkin has been

developed by fusing a sequence-optimized hydrophobic cell-penetrating peptide (CPP), namely advanced
macromolecule transduction domain (aMTD) to Parkin. To demonstrate the therapeutic effect of iCP-Parkin in PD

animal models, 6-OHDA as a neurotoxin was challenged in rats, and various initiation timepoints (day 3-14, 30
mg/kg, 3 times/week for 4 weeks) for iCP-Parkin treatment were investigated. As a result, the treatment of iCP-

Parkin from day 14 after 6-OHDA challenge resulted only 8% of motor function recovery in cylinder test; however,
the motor function was recovered up to 37% when iCP-Parkin was injected from day 10. In addition, iCP-Parkin

showed higher efficacy (cylinder test: 76%) of motor function recovery in rats showing less than 90% of DA damage
in the striatum, when injected at earlier time-point (day 7) after the challenge. Taken together, iCP-Parkin can rescue

damaged neuron with great therapeutic potential as a disease-modifying PD agent.