Page 27 - Q. Neuroscience

A Brain-Deliverable Parkin Rescues Damaged Neurons From Accumulation Of
Pathological α-Synuclein In Pathogenic Road Of Parkinson’s Disease

Junghwan Jo, Hyunji Lee, Sunyoung Hwang, Seongcheol Kim, Seung Woo Lee, So Jung Sung, Eunna Chung, and Daewoong Jo
Neurodegenerative Disease Drug Development Team, Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea.

BACKGROUND AIM
Phosphorylated/aggregated α-Synuclein, marked as Lewy bodies, is Improved Cell-Permeable Parkin (iCP-Parkin) fused to an advanced
remarkably deposited and propagated in substantia nigra under macromolecule transduction domain (aMTD) has been developed to
Parkinson’s Disease (PD) with progressive death of dopaminergic (DA) obtain great neuronal permeability in neurons, penetrating across
neurons. Parkin is an E3 ubiquitin ligase that plays a critical role in the blood-brain barrier (BBB) and removes damaged organelles and
ubiquitination process to remove the pathological α-Synuclein. misfolded proteins.

METHODS
The quantified cell lysates were separated by 10% SDS-PAGE and transferred to nitrocellulose membranes. Membranes were incubated with
primary antibodies against α-Synuclein, TH, pSer 129 -α-Synuclein and β-actin followed by secondary antibodies. immunoblots were quantified
with ImageJ software.
RESULTS

Figure 1. iCP-Parkin Ubiquitinates Known
Parkin Substrates Found In Lewy Body Figure 2. iCP-Parkin Eliminates Pathological α-Synuclein
A B C
A B

D

Figure 3. iCP-Parkin Has Cytoprotective Effect
In Damaged Neuronal Cells Figure 4. iCP-Parkin Reduces α-Synuclein Aggregated Forms Via Both UPS And ALS System
A A B

B

Figure 5. iCP-Parkin Eliminates α-Synuclein Aggregated Forms In PFF-Induced PD Model
C
C D

B

CONCLUSION REFERENCES Contact information
iCP-Parkin suppressed pathogenic α-Synuclein Chung et al. (2020) Science Advances, 6: eaba 1193 Minyong Jung
(91%), and showed cytoprotective activity (94%). Lim et al. (2013) Clinical Cancer Research, 19: 680-690
And also induced ubiquitination of substrates New Drug & Business Development
such as Synuclein-alpha-interacting protein Lim et al. (2013) Biomaterials, 34: 6261-6271 Cellivery Therapeutics, Inc.
(Synphilin-1). These results suggest that iCP- Lim et al. (2012) Molecular Therapy, 20: 1540-1549
Parkin is a potential PD-therapeutic agent as a Jo et al. (2005) Nature Medicine, 11: 892-898 jungmy@cellivery.com
suppressor for pathological α-Synuclein.
Jo et al. (2001) Nature Biotechnology, 19: 929-933 +82-2-3151-8900