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.
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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 |
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