Vinit Raj (중앙대학교) | 한빛사논문 > 한빛사

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중앙대학교

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J. Control. Release, Jan 16 2025, 379 S0168-3659(25)00021-5 | https://doi.org/10.1016/j.jconrel.2025.01.019 Human serum albumin-3-amino-1-propanesulfonic acid conjugate inhibits amyloid-β aggregation and mitigates cognitive decline in Alzheimer's disease

Divya Shastri ^a,c,1, Chaitany Jayprakash Raorane ^b,1, Vinit Raj ^a, Sangkil Lee ^a

^aCollege of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea
^bSchool of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
^cCollege of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-Gu, Daegu 42601, Republic of Korea

¹Authors contributed equally
Corresponding authors : Vinit Raj, Sangkil Lee

Abstract

Alzheimer's disease (AD) is the most commonly occurring brain disorder, characterized by the accumulation of amyloid-β (Aβ) and tau, subsequently leading to neurocognitive decline. 3-Amino-1-propanesulfonic acid (TPS) and its prodrug, currently under clinical trial III, serve as promising therapeutic agents targeting Aβ pathology by specifically preventing monomer-to-oligomer formation. Inspired by the potency of TPS prodrug, we hypothesized that conjugating TPS with human serum albumin (HSA) could enhance brain delivery and synergistically inhibit Aβ aggregation in mild to moderate AD. Thus, we prepared and extensively characterized HSA-TPS (h-TPS) conjugate using an eco-friendly coupling method. In vitro studies on Aβ aggregation kinetics and AFM imaging revealed significant prevention of Aβ aggregation. Additionally, h-TPS significantly reduced Aβ-induced neurotoxicity and H₂O₂-mediated reactive oxygen species (ROS) stress in SH-SY5Y cells. Moreover, h-TPS administration improved blood-brain barrier permeability and cellular uptake into neuronal cells as well as showed in vivo uptake inside the brain within 1 h. In vivo studies using an Aβ_1-42-induced acute AD rat model exhibited a dose-dependent significant reduction in hippocampal Aβ levels and restoration of declined spatial learning and memory with h-TPS treatment. Overall, findings suggest that h-TPS conjugate might be a promising neuroprotective agent for preventing Aβ aggregation in mild to moderate AD.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-22)
연구진국내 연구진
분야 의약학 > 약학

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