Page 28 - Q. Neuroscience

[Q. Neuroscience-16]

A brain-deliverable Parkin rescues damaged neurons from

accumulation of pathological α-Synuclein

Junghwan Jo¹, Hyunji Lee¹, Sunyoung Hwang¹, Seongcheol Kim¹, Seungwoo Lee¹, Sojung Sung¹, Eunna Chung¹,
Youngsil Choi¹, Daewoong Jo¹˙*

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

Phosphorylated/aggregated α-Synuclein, marked as Lewy bodies, is remarkably deposited and propagated in

substantia nigra under the neurodegenerative process of Parkinson’s Disease (PD) with progressive death of
dopaminergic (DA) neurons. Even though Parkin, working as E3 ubiquitin ligase, removes damaged organelles and

misfolded proteins, the accurate involvement of Parkin in PD pathogenic process remains unclear. Improved cell-
permeable Parkin (iCP-Parkin) fused to a sequence-optimized advanced macromolecule transduction domain (aMTD)

has been developed to obtain great neuronal permeability in neurons, penetrating across blood-brain barrier (BBB).
In α-Synuclein-overexpressing cells treated with neurotoxin (sodium arsenite), iCP-Parkin suppressed pathogenic α-

Synuclein (91%), and showed cytoprotective activity (94%). Furthermore, iCP-Parkin also was induced ubiquitination
of substrates such as Parkin-related endothelin receptor-like receptor (Pael-R) and Synuclein-alpha-interacting

protein (Synphilin-1), which are involved in formation of Lewy body. These results suggest that iCP-Parkin is a
potential PD-therapeutic agent as a powerful suppressor for pathological α-Synuclein.