Abstract
The two major neuropathologic hallmarks of AD are extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with Aβ plaques and NFTs formation, have been described, including inflammation, oxidative damage, iron dysregulation, and alterations in cholesterol metabolism. In this review, all of these mechanisms will be discussed and treatments that are under development to interfere with these pathogenic steps will be presented. A primary goal of work in this area is identification of novel compounds that can block the course of the disease in early phases. For this reason they are currently termed “disease modifying” drugs. These drugs are designed to modify pathological steps leading to AD, thus acting on the evolution and progression of the disease. Some of these molecules are undergoing clinical testing whereas others are in preclinical phases of development. Several approaches have been considered, including mainly Aβ deposition interference by anti- Aβ aggregation agents, vaccination, γ-secretase inhibition or selective Aβ42-lowering agents (SALAs), tau deposition interference by methyl thioninium chloride (MTC), and methods for reduction of inflammation and oxidative damage.
Keywords: Alzheimer's disease, amyloid, tau, inflammation, disease-modifying drugs, anti-inflammatories
CNS & Neurological Disorders - Drug Targets
Title: Alzheimers Disease: From Pathogenesis to Disease-Modifying Approaches
Volume: 10 Issue: 2
Author(s): Daniela Galimberti and Elio Scarpini
Affiliation:
Keywords: Alzheimer's disease, amyloid, tau, inflammation, disease-modifying drugs, anti-inflammatories
Abstract: The two major neuropathologic hallmarks of AD are extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with Aβ plaques and NFTs formation, have been described, including inflammation, oxidative damage, iron dysregulation, and alterations in cholesterol metabolism. In this review, all of these mechanisms will be discussed and treatments that are under development to interfere with these pathogenic steps will be presented. A primary goal of work in this area is identification of novel compounds that can block the course of the disease in early phases. For this reason they are currently termed “disease modifying” drugs. These drugs are designed to modify pathological steps leading to AD, thus acting on the evolution and progression of the disease. Some of these molecules are undergoing clinical testing whereas others are in preclinical phases of development. Several approaches have been considered, including mainly Aβ deposition interference by anti- Aβ aggregation agents, vaccination, γ-secretase inhibition or selective Aβ42-lowering agents (SALAs), tau deposition interference by methyl thioninium chloride (MTC), and methods for reduction of inflammation and oxidative damage.
Export Options
About this article
Cite this article as:
Galimberti Daniela and Scarpini Elio, Alzheimers Disease: From Pathogenesis to Disease-Modifying Approaches, CNS & Neurological Disorders - Drug Targets 2011; 10 (2) . https://dx.doi.org/10.2174/187152711794480438
DOI https://dx.doi.org/10.2174/187152711794480438 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Bacteriocins Active Against Multi-Resistant Gram Negative Bacteria Implicated in Nosocomial Infections
Infectious Disorders - Drug Targets Chemical Libraries Towards Protein Kinase Inhibitors
Combinatorial Chemistry & High Throughput Screening miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets Biotechnological Approaches for the Treatment of Inflammatory Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Morpho-Functional Features of In-Vitro Cell Death Induced by Physical Agents
Current Pharmaceutical Design Cellular Therapy of Lysosomal Storage Disorders: Current Status and Future Prospects
Current Pediatric Reviews Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Translational Gap in Glioma Research
Anti-Cancer Agents in Medicinal Chemistry 5q- syndrome
Current Pharmaceutical Design Sirtuin Modulators: Mechanisms and Potential Clinical Implications
Current Medicinal Chemistry Accessing Cancer Metabolic Pathways by the Use of Microarray Technology
Current Pharmaceutical Design Bladder Cancer and Stem Cells
Current Signal Transduction Therapy Airway Smooth Muscle Responsiveness: The Origin of Airway Hyperresponsiveness in Asthma?
Current Respiratory Medicine Reviews The Role of Antihistamine Drugs in Allergic Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics Transplacental Transfer of Immunosuppressants and Biologics Used for the Treatment of Inflammatory Bowel Disease
Current Pharmaceutical Biotechnology Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia
Protein & Peptide Letters Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Anti-Cancer Agents in Medicinal Chemistry FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract
Current Drug Targets