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Current and emerging avenues for Alzheimer's disease drug targets
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Loera‐Valencia, R., Cedazo‐Minguez, A., Kenigsberg, P., Page, G., Duarte, A., Giusti, P., Zusso, M., Robert, P., Frisoni, G. B., Cattaneo, A., Zille, M., Boltze, Johannes, Cartier, N., Buee, l., Johansson, G. and Winblad, B. (2019) Current and emerging avenues for Alzheimer's disease drug targets. Journal of Internal Medicine, 286 (4). pp. 398-437. doi:10.1111/joim.12959 ISSN 1365-2796.
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Official URL: https://doi.org/10.1111/joim.12959
Abstract
Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic and so far, there is no cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described: amyloid beta (Aβ) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation, and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and non‐pharmacological approaches including gene therapy. We propose that AD could be tackled using combination therapies including Aβ and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood‐brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near‐future strategy.
| Item Type: | Journal Article | |||||||||||||||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||
| SWORD Depositor: | Library Publications Router | |||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Alzheimer's disease -- Treatment -- Research, Alzheimer's disease, Alzheimer's disease -- Molecular aspects | |||||||||||||||||||||||||||
| Journal or Publication Title: | Journal of Internal Medicine | |||||||||||||||||||||||||||
| Publisher: | Wiley | |||||||||||||||||||||||||||
| ISSN: | 1365-2796 | |||||||||||||||||||||||||||
| Official Date: | October 2019 | |||||||||||||||||||||||||||
| Dates: |
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| Volume: | 286 | |||||||||||||||||||||||||||
| Number: | 4 | |||||||||||||||||||||||||||
| Page Range: | pp. 398-437 | |||||||||||||||||||||||||||
| DOI: | 10.1111/joim.12959 | |||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||
| Reuse Statement (publisher, data, author rights): | "This is the peer reviewed version of the following article: Loera‐Valencia, R. , Cedazo‐Minguez, A. , Kenigsberg, P. , Page, G. , Duarte, A. , Giusti, P. , Zusso, M. , Robert, P. , Frisoni, G. , Cattaneo, A. , Zille, M. , Boltze, J. , Cartier, N. , Buee, l. , Johansson, G. and Winblad, B. (2019), Current and emerging avenues for Alzheimer's disease drug targets. J Intern Med. which has been published in final form at https://doi.org/10.1111/joim.12959. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions." | |||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||
| Description: | Free access |
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| Date of first compliant deposit: | 23 July 2019 | |||||||||||||||||||||||||||
| Date of first compliant Open Access: | 8 July 2020 | |||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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