Emani Lakshmi Sowmya, Rao Jayanth K, Kumar Dasappa Jagadeesha, Pecchio Marisín, Lakey-Beitia Johant, Rodriguez Hansapani, Cruz-Mora Jessica, Narayan Priya, Anand Nikhilesh, Mullur Govindaraju, Ajumeera Rajanna, Gadad Bharathi S, Kosagisharaf Jagannatha Rao
Department of Biotechnology, KLEF Deemed to be University, Vijayawada, India.
Graduate Medical Student, School of Medicine, University College of Dublin, Dublin, Ireland.
J Alzheimers Dis Rep. 2025 Jun 9;9:25424823251347260. doi: 10.1177/25424823251347260. eCollection 2025 Jan-Dec.
α-synuclein (α-syn) deposition in the mid-brain region is one of the hallmark pathologies of Parkinson's disease (PD). The key steps involve the transformation of α-synuclein into a toxic oligomer and insoluble fibrillar aggregates.
To understand the role of curcumin-glucoside in the prevention of α-syn aggregation, a mechanistic approach.
In the present study, we synthesized a novel molecule, curcumin-glucoside (Curc-gluc), to improve the water solubility and partition coefficient, making the molecule with high bioavailability. The present study is focused on understanding the α-syn aggregation kinetics in the presence and absence of Curc-gluc, curcumin (Cur), copper (Cu), and iron (Fe) through Thioflavin T analysis, circular dichroism (CD), mathematical approach by self-association kinetics, and molecular docking models.
The results indicated that Curc-gluc potentially prevented synuclein aggregation compared to Curc alone and inhibited Cu and Fe-induced synuclein aggregation. CD studies indicated that Curc-gluc favored α-helix formation. The docking studies indicated that Curc-gluc derivatives interacted with various chains of α-syn fibrils, namely G-chain, A-chain, I-Chain, and E-chain and the Pi-Pi interaction indicate that, Curc-gluc shows the most favorable binding affinity with the α-syn fibrils with 60.7222 kcal/mol of -CDOCKER_ ENERGY and 89.6516 kcal/mol of -CDOCKER INTERACTION_ ENERGY. The Absorption, Distribution, Metabolism, Excretion (ADME) analysis indicated that Curc-mono and di-gluc have the highest solubility, bioavailability, and tissue distribution compared to Curc alone.
The studies indicated that Curc-gluc prevented α-syn aggregation by favoring α-helix, binding to α-syn, and preventing aggregation, and had high bioavailability.
α-突触核蛋白（α-syn）在中脑区域的沉积是帕金森病（PD）的标志性病理特征之一。关键步骤包括α-突触核蛋白转化为有毒的寡聚体和不溶性纤维状聚集体。
采用一种机制性方法来了解姜黄素葡糖苷在预防α-syn聚集方面的作用。
在本研究中，我们合成了一种新型分子姜黄素葡糖苷（Curc-gluc），以提高其水溶性和分配系数，使该分子具有高生物利用度。本研究的重点是通过硫黄素T分析、圆二色性（CD）、自缔合动力学的数学方法以及分子对接模型，了解在有和没有Curc-gluc、姜黄素（Cur）、铜（Cu）和铁（Fe）存在的情况下α-syn的聚集动力学。
结果表明，与单独的姜黄素相比，Curc-gluc可能预防突触核蛋白聚集，并抑制Cu和Fe诱导的突触核蛋白聚集。CD研究表明，Curc-gluc有利于α-螺旋的形成。对接研究表明，Curc-gluc衍生物与α-syn纤维的各种链相互作用，即G链、A链、I链和E链，并且π-π相互作用表明，Curc-gluc与α-syn纤维表现出最有利的结合亲和力，其-CDOCKER_ENERGY为60.7222千卡/摩尔，-CDOCKER_INTERACTION_ENERGY为89.6516千卡/摩尔。吸收、分布、代谢、排泄（ADME）分析表明，与单独的姜黄素相比，单葡糖和二葡糖形式的姜黄素具有最高的溶解度、生物利用度和组织分布。
研究表明，Curc-gluc通过促进α-螺旋形成、与α-syn结合并防止聚集来预防α-syn聚集，并且具有高生物利用度。
