Abstract
Numerous studies have indicated that Alzheimers amyloid-β protein (Aβ) causes the degeneration of synapses and neurons, finally inducing the pathogenesis of Alzheimers disease (AD). Recent approaches have emphasized the importance of Aβ oligomerization which enhances its neurotoxicity and synaptotoxicity. Our work as well as other groups research have demonstrated that Aβ oligomers are directly incorporated into neuronal membranes and form calcium-permeable ion channels (amyloid channels). Although the precise molecular mechanism of Aβ neurotoxicity remains elusive, the formation of amyloid channels and the resultant abnormal elevation of the intracellular calcium levels might be the primary event for neurodegeneration, considering that calcium dyshomeostasis triggers various apoptotic pathways. This article reviews the current understanding of AD pathology based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of Aβ neurotoxicity. The potential development of preventive agents for new therapeutic targets is also discussed.
Keywords: Oligomerization, synaptotoxicity, zinc, aluminum, neurosteroids, apoptosis, membrane fluidity, Aamyloid-b protein, Alzheimer's disease, Ion channels, Amyloid channels, Neurodegeneration, Dyshomeostasis, Dementia, Memory loss, Senile plaques, Neurofibrillary tangles, Prion disease, Parkinson's disease, Huntington's disease, Presenilins, Ca2+ homeostasis, Chromatography, gel electrophoresis, Atomic force microscopy, Transthyletin, Rifampicin, Curcumin, Aspirin, Polymerization, Ca2+ channels, Xenopus oocytes, Tetrodotoxin, Nifedipine, D-APV, Bicuculline, Chelation therapy, Clioquinol, deferoxamine
Current Pharmaceutical Design
Title: Neurotoxicity of β-Amyloid Protein: Oligomerization, Channel Formation and Calcium Dyshomeostasis
Volume: 16 Issue: 25
Author(s): Masahiro Kawahara
Affiliation:
Keywords: Oligomerization, synaptotoxicity, zinc, aluminum, neurosteroids, apoptosis, membrane fluidity, Aamyloid-b protein, Alzheimer's disease, Ion channels, Amyloid channels, Neurodegeneration, Dyshomeostasis, Dementia, Memory loss, Senile plaques, Neurofibrillary tangles, Prion disease, Parkinson's disease, Huntington's disease, Presenilins, Ca2+ homeostasis, Chromatography, gel electrophoresis, Atomic force microscopy, Transthyletin, Rifampicin, Curcumin, Aspirin, Polymerization, Ca2+ channels, Xenopus oocytes, Tetrodotoxin, Nifedipine, D-APV, Bicuculline, Chelation therapy, Clioquinol, deferoxamine
Abstract: Numerous studies have indicated that Alzheimers amyloid-β protein (Aβ) causes the degeneration of synapses and neurons, finally inducing the pathogenesis of Alzheimers disease (AD). Recent approaches have emphasized the importance of Aβ oligomerization which enhances its neurotoxicity and synaptotoxicity. Our work as well as other groups research have demonstrated that Aβ oligomers are directly incorporated into neuronal membranes and form calcium-permeable ion channels (amyloid channels). Although the precise molecular mechanism of Aβ neurotoxicity remains elusive, the formation of amyloid channels and the resultant abnormal elevation of the intracellular calcium levels might be the primary event for neurodegeneration, considering that calcium dyshomeostasis triggers various apoptotic pathways. This article reviews the current understanding of AD pathology based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of Aβ neurotoxicity. The potential development of preventive agents for new therapeutic targets is also discussed.
Export Options
About this article
Cite this article as:
Kawahara Masahiro, Neurotoxicity of β-Amyloid Protein: Oligomerization, Channel Formation and Calcium Dyshomeostasis, Current Pharmaceutical Design 2010; 16 (25) . https://dx.doi.org/10.2174/138161210793176545
DOI https://dx.doi.org/10.2174/138161210793176545 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Protein Kinase CK2 in Human Diseases
Current Medicinal Chemistry Molecule of the Month
Current Topics in Medicinal Chemistry The Effect of PAOPA, a Novel Allosteric Modulator of Dopamine D2 Receptors, on Signaling Proteins Following Sub-Chronic Administration in Rats
Current Molecular Pharmacology <i>Lepidium meyenii</i> Supplemented Diet Modulates Neurobehavioral and Biochemical Parameters in Mice Fed High-Fat High-Sugar Diet
Endocrine, Metabolic & Immune Disorders - Drug Targets Multi-targeting the Entrance Door to Block HIV-1
Current Drug Targets - Infectious Disorders Glycosphingolipid Structure and Function in Membranes
Current Organic Chemistry Extracellular Ca<sup>2+</sup> Selectively Enhances Adriamycin-induced Cell Death in Human Hepatoma Cells
Current Cancer Drug Targets Is C-Peptide Replacement the Missing Link for Successful Treatment of Neurological Complications in Type 1 Diabetes?
Current Drug Targets Diagnostic and Therapeutic Uses of Nanomaterials in the Brain
Current Medicinal Chemistry Aurora Kinase Inhibitors in Head and Neck Cancer
Current Topics in Medicinal Chemistry Inhibition of Tau Protein Aggregation by Rhodanine-based Compounds Solubilized Via Specific Formulation Additives to Improve Bioavailability and Cell Viability
Current Alzheimer Research Kinases as Targets for Parkinson's Disease: From Genetics to Therapy
CNS & Neurological Disorders - Drug Targets Extracellular Targeting of Synthetic Therapeutic Nucleic Acid Formulations
Current Gene Therapy Targeting the Resistance of Pancreatic Cancer Cells to Nutrient Deprivation: Anti-Austerity Compounds
Current Drug Delivery PROTACs: Promising Approaches for Epigenetic Strategies to Overcome Drug Resistance
Current Cancer Drug Targets Molecular Basis for the Neuroprotective Properties of FKBP-Binding Immunophilin Ligands
Current Medicinal Chemistry - Central Nervous System Agents Interventional Radiology in Paediatrics
Current Pediatric Reviews Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer’s Disease
Current Neuropharmacology New Insights into Serotonin 5-HT4 Receptors : A Novel Therapeutic Target for Alzheimers Disease?
Current Alzheimer Research Molecular Chaperone Activity and Biological Regulatory Actions of the TPR-Domain Immunophilins FKBP51 and FKBP52
Current Protein & Peptide Science