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
-
Targeting Heat Shock Proteins 70/90 and Proteasome for Cancer Therapy
Current Medicinal Chemistry Imatinib Mesylate for the Treatment of Solid Tumours: Recent Trials and Future Directions
Current Enzyme Inhibition Gene Therapy for Brain Cancer: Combination Therapies Provide Enhanced Efficacy and Safety
Current Gene Therapy The Diterpenoids of the Genus Elaeoselinum (Apiaceae) and their Biological Properties
Current Organic Chemistry Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity
Current Medicinal Chemistry New Molecular Targets of Anticancer Therapy – Current Status and Perspectives
Current Medicinal Chemistry Valproic Acid As Anti-Cancer Drug
Current Pharmaceutical Design Therapeutic Potential of Endophytic Compounds: A Special Reference to Drug Transporter Inhibitors
Current Topics in Medicinal Chemistry Epigenetic Interventions Increase the Radiation Sensitivity of Cancer Cells
Current Pharmaceutical Design Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders
Current Pharmaceutical Design Targeting the Immune Niche within the Bone Marrow Microenvironment: The Rise of Immunotherapy in Multiple Myeloma
Current Cancer Drug Targets Mechanism of Cancer Drug Resistance and the Involvement of Noncoding RNAs
Current Medicinal Chemistry Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy
Current Medicinal Chemistry Newer Avenues for the Treatment of Leptomeningeal Carcinomatosis
Central Nervous System Agents in Medicinal Chemistry Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics Editorial [Hot topic: The Urokinase Receptor System as Strategic Therapeutic Target: Challenges for the 21st Century (Executive Guest Editor: Bernard Degryse)]
Current Pharmaceutical Design World Health Organization Classification of Myelodysplastic Syndromes
Current Pharmaceutical Design Pharma-metabolomics in Neonatology: is it a Dream or a Fact?
Current Pharmaceutical Design Tumor Targeted Therapies: Strategies for Killing Cancer but not Normal Cells
Current Cancer Therapy Reviews New Drugs, Therapeutic Strategies, and Future Direction for the Treatment of Pulmonary Arterial Hypertension
Current Medicinal Chemistry