Abstract
Amyloid beta (Aβ) protein is the key component of amyloid plaques in Alzheimers disease brain whereas stefin B is an intracellular cysteine proteinase inhibitor, broadly distributed in different tissue and recently reported to form amyloid fibrils in vitro. By reducing the pH to 4.6, the native conformation of both polypeptides are changed into less ordered metastable intermediates that are stabilized by formation of the more stable fibrils. In Aβ, the Glu at position 11 was found to be responsible for the conformational change at pH 4.6. Metal ions, including copper and zinc, could also induce conformational changes of Aβ at neutral pH. The acid modified Aβ conformer exhibited protease K resistance, preferential internalization and accumulation in the human glial cells. In stefin B, reducing the pH to pH 3.3 results in another intermediate of the moltenglobule type which also leads to amyloid fibril formation. Multiple sequence alignment revealed distinct similarities of Aβ (1-42) peptide, stefin B (13 to 61 residues) and prion fragment (90 to 144 residues).
Keywords: Amyloid, metal ions, protease resistance, stefin B, cystatins, molten globule, amyloidfibrillogenesis
Current Medicinal Chemistry
Title: Conformational Changes Preceding Amyloid-fibril Formation of Amyloid-beta and Stefin B; Parallels in pH Dependence
Volume: 9 Issue: 19
Author(s): Yoichi Matsunaga, Eva Zerovnik, Tatsuo Yamada and Vito Turk
Affiliation:
Keywords: Amyloid, metal ions, protease resistance, stefin B, cystatins, molten globule, amyloidfibrillogenesis
Abstract: Amyloid beta (Aβ) protein is the key component of amyloid plaques in Alzheimers disease brain whereas stefin B is an intracellular cysteine proteinase inhibitor, broadly distributed in different tissue and recently reported to form amyloid fibrils in vitro. By reducing the pH to 4.6, the native conformation of both polypeptides are changed into less ordered metastable intermediates that are stabilized by formation of the more stable fibrils. In Aβ, the Glu at position 11 was found to be responsible for the conformational change at pH 4.6. Metal ions, including copper and zinc, could also induce conformational changes of Aβ at neutral pH. The acid modified Aβ conformer exhibited protease K resistance, preferential internalization and accumulation in the human glial cells. In stefin B, reducing the pH to pH 3.3 results in another intermediate of the moltenglobule type which also leads to amyloid fibril formation. Multiple sequence alignment revealed distinct similarities of Aβ (1-42) peptide, stefin B (13 to 61 residues) and prion fragment (90 to 144 residues).
Export Options
About this article
Cite this article as:
Matsunaga Yoichi, Zerovnik Eva, Yamada Tatsuo and Turk Vito, Conformational Changes Preceding Amyloid-fibril Formation of Amyloid-beta and Stefin B; Parallels in pH Dependence, Current Medicinal Chemistry 2002; 9 (19) . https://dx.doi.org/10.2174/0929867023369097
DOI https://dx.doi.org/10.2174/0929867023369097 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells
Current Medicinal Chemistry Treatment of Alzheimers Disease: Symptomatic and Disease-Modifying Approaches
Current Aging Science Dual Inhibition of DPP-4 and Cholinesterase Enzymes by the Phytoconstituents of the Ethanolic Extract of Prosopis cineraria Pods: Therapeutic Implications for the Treatment of Diabetes-associated Neurological Impairments
Current Alzheimer Research Bacterial Toxins: A Hope Towards Angiogenic Ailments
Current Drug Metabolism 1950 MHz Electromagnetic Fields Ameliorate Aβ Pathology in Alzheimer’s Disease Mice
Current Alzheimer Research Vitamin D and the Metabolic Syndrome
Current Vascular Pharmacology A Healthy Gut for a Healthy Brain: Preclinical, Clinical and Regulatory Aspects
Current Neuropharmacology Paullones as Inhibitors of Protein Kinases
Current Topics in Medicinal Chemistry New Insights into Vitamin D and Autophagy in Inflammatory Bowel Diseases
Current Medicinal Chemistry Predicting Monoamine Oxidase Inhibitory Activity Through Ligand-Based Models
Current Topics in Medicinal Chemistry Management of Glia-Mediated Neuroinflammation and Related Patents
Recent Patents on Inflammation & Allergy Drug Discovery Lipid-Based Nanocarriers for CNS-Targeted Drug Delivery
Recent Patents on CNS Drug Discovery (Discontinued) Synthesis and Antimicrobial Activity of Novel 1, 2, 4-Triazolopyrimidofuroquinazolinones from Natural Furochromones (Visnagenone and Khellinone)
Medicinal Chemistry Xanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme
Current Medicinal Chemistry Alzheimers Disease: Pathological Mechanisms and Recent Insights
Current Neuropharmacology Current Concepts in the Understanding of Pain in the Rheumatic Diseases
Current Rheumatology Reviews Cognitive Impairment with Vascular Impairment and Degeneration
Current Neurovascular Research Recent Developments in Cholinesterases Inhibitors for Alzheimers Disease Treatment
Current Medicinal Chemistry Driving Cellular Plasticity and Survival Through the Signal Transduction Pathways of Metabotropic Glutamate Receptors
Current Neurovascular Research Anti-Cancer Effects of Citalopram on Hepatocellular Carcinoma Cells Occur via Cytochrome C Release and the Activation of NF-kB
Anti-Cancer Agents in Medicinal Chemistry