Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain associated with memory impairment, progressive cognitive decline and changes in personality and behavior, with rising incidence among elderly people. Reflecting the world population ageing, the scenario is expected to worsen in the next decades if novel drugs or mechanisms that help to counteract neurodegeneration will not be identified. The complex neuropathology of AD is characterized by cholinergic loss, extracellular deposition of amyloid-β plaques, formation of intracellular neurofibrillary tangles, chronic brain inflammation and oxidative damage. To date, there are no effective treatments that can slow or halt the disease, and currently approved drugs only seem to act as palliative by temporary ameliorating cognitive impairment. On the other hand, the role played by other biological systems in the pathogenetic process is now clearly growing and, as knowledge on how AD develops and triggers brain damage proceeds, drug discovery attempts to identify new potential therapeutic targets. This review will focus on these emerging strategies, some of which could open new therapeutic perspectives in Alzheimer’s disease, adding new elements for the medicinal chemist to handle and combine for the design of novel multi-target-directed ligands able to simultaneously modulate ‘old classic’ and newly identified targets.
Keywords: Alzheimer’s disease, amyloid beta peptide, endocannabinoid system, epigenetic modulation, HAT, HDAC, PDE, PPARγ.
Current Topics in Medicinal Chemistry
Title:Emerging Targets in Neurodegeneration: New Opportunities for Alzheimer's Disease Treatment?
Volume: 13 Issue: 15
Author(s): Angela Rampa, Silvia Gobbi, Federica Belluti and Alessandra Bisi
Affiliation:
Keywords: Alzheimer’s disease, amyloid beta peptide, endocannabinoid system, epigenetic modulation, HAT, HDAC, PDE, PPARγ.
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain associated with memory impairment, progressive cognitive decline and changes in personality and behavior, with rising incidence among elderly people. Reflecting the world population ageing, the scenario is expected to worsen in the next decades if novel drugs or mechanisms that help to counteract neurodegeneration will not be identified. The complex neuropathology of AD is characterized by cholinergic loss, extracellular deposition of amyloid-β plaques, formation of intracellular neurofibrillary tangles, chronic brain inflammation and oxidative damage. To date, there are no effective treatments that can slow or halt the disease, and currently approved drugs only seem to act as palliative by temporary ameliorating cognitive impairment. On the other hand, the role played by other biological systems in the pathogenetic process is now clearly growing and, as knowledge on how AD develops and triggers brain damage proceeds, drug discovery attempts to identify new potential therapeutic targets. This review will focus on these emerging strategies, some of which could open new therapeutic perspectives in Alzheimer’s disease, adding new elements for the medicinal chemist to handle and combine for the design of novel multi-target-directed ligands able to simultaneously modulate ‘old classic’ and newly identified targets.
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Cite this article as:
Rampa Angela, Gobbi Silvia, Belluti Federica and Bisi Alessandra, Emerging Targets in Neurodegeneration: New Opportunities for Alzheimer's Disease Treatment?, Current Topics in Medicinal Chemistry 2013; 13 (15) . https://dx.doi.org/10.2174/15680266113139990143
DOI https://dx.doi.org/10.2174/15680266113139990143 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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