Page 28 - ebook

[A. Biochemistry/Molecular Biology] A-14

Improved Cell-Permeable Parkin Is A Potent Therapeutics For

Elimination Of β-Amyloid Fibril In Alzheimer’s Disease

Dementia

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Sujeong Kim¹ , Sangsun Yoon¹ , Joonno Lee¹, Dongjae Min¹, Seungwoo Lee¹, Sojung Sung¹,
#
Eunna Chung¹, Daewoong Jo¹*

¹Neurodegenerative Diseases (NDD) Team, Cellivery Therapeutics, Inc., Seoul 03929, Korea

β-Amyloid (Aβ) is a pathological hallmark of Alzheimer’s disease (AD) can cause dysfunction and death of neurons

in brain, where pathogenesis of AD mainly happens. To deliver therapeutic neuroprotective molecules into target
neurons without direct injection, one should be able to penetrate the Blood-Brain Barrier (BBB). Improved cell-

permeable Parkin (iCP-Parkin) has been developed by fusing a sequence-optimized hydrophobic cell-penetrating
peptide (CPP) to endogenous human Parkin protein. It has been demonstrated that 1) iCP-Parkin was delivered into

neuronal cells localized in the deep brain, and 2) protected neurons by suppressing accumulation of damaged Aβ
in hippocampus, consequently exerting reversible recovery of cognitive in Aβ-induced AD animals. The goal of this

study is to expand the therapeutic scope of iCP-Parkin toward the AD field via a preclinical development. iCP-Parkin
showed up to 91% recovery of cognitive defects compared to the Aβ induced AD group in the Y-maze test. In

addition, iCP-Parkin reduced up to 86% of Aβ plaque expression after Aβ induction. In further study, we will explore
the localization of iCP-Parkin in Aβ-indcued AD animals brain. Finally, iCP-Parkin will be developed as a novel

neuroprotective therapy for dementia in AD.