The Role of Glycosaminoglycan Sulfation in the Formation of Immunoglobulin Light Chain Amyloid Oligomers and Fibrils
نویسندگان
چکیده
Ruiyi Ren, Zhenning Hong, Haiyan Gong, Kate Laporte, Martha Skinner, David C. Seldin, Catherine E. Costello, Lawreen H. Connors and Vickery Trinkaus-Randall The Departments of Anatomy and Neurobiology, Biochemistry, Medicine, Ophthalmology, the Amyloid Treatment and Research Program, and the Mass Spectrometry Resource Boston University School of Medicine, Boston, Massachusetts 02118 Running head: AL fibrils: role of GAGs Address correspondence to: Vickery Trinkaus-Randall, Ph.D., Boston University School of Medicine, 80 E Concord St L904, Boston, MA 02118. TEL: 617-638-5099; FAX: 617-638-5339; Email: [email protected]
منابع مشابه
Role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils.
Primary amyloidosis (AL) results from overproduction of unstable monoclonal immunoglobulin light chains (LCs) and the deposition of insoluble fibrils in tissues, leading to fatal organ disease. Glycosaminoglycans (GAGs) are associated with AL fibrils and have been successfully targeted in the treatment of other forms of amyloidosis. We investigated the role of GAGs in LC fibrillogenesis. Ex viv...
متن کاملInhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain
Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. ...
متن کاملInhibitory Effect of Cinnamomum Zeylanicum and Camellia Sinensis Extracts on the Hen EggWhite Lysozyme Fibrillation
Background & Aims: Many neurodegenerative diseases including Alzheimer’s, Parkinson and Huntington diseases are associated with the deposition proteinaceous aggregates known as amyloid fibrils. Currently, there is no approved therapeutic agent for inhibition of fibrillar assemblies. One important approach in the development of therapeutic agents is the use of herbal extracts. At the present com...
متن کاملStudy of Cis–trans Isomerization Mechanism of [3-(3-Aminomethyl) Phenylazo] Phenyl Acetic Acid as a Causative Role in Alzheimer Using Density Functional Theory
Amyloid-β (Aβ) self-assembly into cross-β amyloidfibrils is implicated in a causative role in Alzheimer’s disease pathology.Uncertainties persist regarding the mechanisms of amyloid self assembly and the role of metastable prefibrillar aggregates. Aβ fibrilsfeature a sheet-turn-sheet motif in the constituent β-strands; as such, turn nucleation has been proposed as a rate-limiting step in the se...
متن کاملStudy of Cis–trans Isomerization Mechanism of [3-(3-Aminomethyl) Phenylazo] Phenyl Acetic Acid as a Causative Role in Alzheimer Using Density Functional Theory
Amyloid-β (Aβ) self-assembly into cross-β amyloidfibrils is implicated in a causative role in Alzheimer’s disease pathology.Uncertainties persist regarding the mechanisms of amyloid self assembly and the role of metastable prefibrillar aggregates. Aβ fibrilsfeature a sheet-turn-sheet motif in the constituent β-strands; as such, turn nucleation has been proposed as a rate-limiting step in the se...
متن کامل