Bloch Daniel Nir, Sandre Michele, Ben Zichri Shani, Masato Anna, Kolusheva Sofiya, Bubacco Luigi, Jelinek Raz
Department of Chemistry, Ben Gurion University of the Negev Israel
Department of Neuroscience, University of Padova Italy.
Nanoscale Adv. 2023 Jan 19;5(5):1356-1367. doi: 10.1039/d2na00804a. eCollection 2023 Feb 28.
Reactive aldehydes generated in cells and tissues are associated with adverse physiological effects. Dihydroxyphenylacetaldehyde (DOPAL), the biogenic aldehyde enzymatically produced from dopamine, is cytotoxic, generates reactive oxygen species, and triggers aggregation of proteins such as α-synuclein implicated in Parkinson's disease. Here, we demonstrate that carbon dots (C-dots) prepared from lysine as the carbonaceous precursor bind DOPAL molecules through interactions between the aldehyde units and amine residues on the C-dot surface. A set of biophysical and experiments attests to attenuation of the adverse biological activity of DOPAL. In particular, we show that the lysine-C-dots inhibit DOPAL-induced α-synuclein oligomerization and cytotoxicity. This work underlines the potential of lysine-C-dots as an effective therapeutic vehicle for aldehyde scavenging.
细胞和组织中产生的反应性醛类与不良生理效应相关。二羟基苯乙醛(DOPAL)是由多巴胺酶促产生的生物源醛,具有细胞毒性,会产生活性氧,并引发与帕金森病相关的蛋白质(如α-突触核蛋白)聚集。在此,我们证明以赖氨酸为碳质前体制备的碳点(C点)通过醛基单元与C点表面胺残基之间的相互作用结合DOPAL分子。一系列生物物理和实验证明了DOPAL不良生物活性的减弱。特别是,我们表明赖氨酸-C点可抑制DOPAL诱导的α-突触核蛋白寡聚化和细胞毒性。这项工作强调了赖氨酸-C点作为醛清除有效治疗载体的潜力。