Biomaterial Database

Menadione sodium bisulfite inhibits the toxic aggregation of amyloid-β(1-42). 2018

Yu Zhang, and Yudan Zhao, and Zhuoyi Wang, and Hao Gong, and Liang Ma, and Dongsheng Sun, and Chen Yang, and Yang Li, and Biao Cheng, and Robert B Petersen, and Fengchao Jiang, and Gongping Liu, and Kun Huang

Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Protein misfolding and aggregation are associated with amyloidosis. The toxic aggregation of amyloid-β 1-42 (Aβ42) may disrupt cell membranes and lead to cell death and is thus regarded as a contributing factor in Alzheimer's disease (AD). 1,4-naphthoquinone (NQ) has been shown to exhibit strong anti-aggregation effects on amyloidogenic proteins such as insulin and α-synuclein; however, its high toxicity and poor solubility limit its clinical application. Menadione sodium bisulfite (MSB, also known as vitamin K3), is used clinically in China to treat hemorrhagic diseases caused by vitamin K deficiency and globally as a vitamin K supplement. We hypothesized that MSB could inhibit amyloid formation since its backbone structure is similar to NQ. To test our hypothesis, we first investigated the effects of MSB on Aβ42 amyloid formation in vitro. We found that MSB inhibited Aβ42 amyloid formation in a dose dependent manner, delayed the secondary structural conversion of Aβ42 from random coil to ordered β-sheet, and attenuated the ability of Aβ42 aggregates to disrupt membranes; moreover, the quinone backbone rather than lipophilicity is esstial for the inhibitory effects of MSB. Next, in cells expressing a pathogenic APP mutation (Osaka mutation) that results in the formation of intraneuronal Aβ oligomers, MSB inhibited the intracellular aggregation of Aβ. Moreover, MSB treatment significantly extended the life span of Caenorhabditis elegans CL2120, a strain that expresses human Aβ42. Together, these results suggest that MSB and its derivatives may be further explored as potential therapeutic agents for the prevention or treatment of AD.

UI	MeSH Term	Description	Entries
D008136	Longevity	The normal length of time of an organism's life.	Length of Life,Life Span,Lifespan,Life Spans,Lifespans
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014815	Vitamins	Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.	Vitamin
D016229	Amyloid beta-Peptides	Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.	Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D017173	Caenorhabditis elegans	A species of nematode that is widely used in biological, biochemical, and genetic studies.	Caenorhabditis elegan,elegan, Caenorhabditis
D024483	Vitamin K 3	A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.	Menadione,2-Methyl-1,4-naphthalenedione,2-Methyl-1,4-naphthoquinone,2-Methylnaphthoquinone,Menadione Bisulfite,Menadione Sodium Bisulfite,Menadione Sodium Bisulfite, Trihydrate,Vicasol,Vikasol,Vitamin K3,Vitamin K3 Sodium Bisulfite,Bisulfite, Menadione,Bisulfite, Menadione Sodium,Sodium Bisulfite, Menadione
D030801	Animals, Genetically Modified	ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.	Animals, Transgenic,Genetically Modified Animals,Transgenic Animals,Founder Animals, Transgenic,GMO Animals,Genetically Engineered Animals,Animal, GMO,Animal, Genetically Engineered,Animal, Genetically Modified,Animal, Transgenic,Animal, Transgenic Founder,Animals, GMO,Animals, Genetically Engineered,Animals, Transgenic Founder,Engineered Animal, Genetically,Engineered Animals, Genetically,Founder Animal, Transgenic,GMO Animal,Genetically Engineered Animal,Genetically Modified Animal,Modified Animal, Genetically,Modified Animals, Genetically,Transgenic Animal,Transgenic Founder Animal,Transgenic Founder Animals
D066263	Protein Aggregation, Pathological	A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION; POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.	Aggregation, Pathological Protein,Pathological Protein Aggregation