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New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease
Open accessAbstract
As the population ages, Alzheimer's disease (AD), the most common neurodegenerative disease in elderly people, will impose social and economic burdens to the world. Currently approved drugs for the treatment of AD including cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and an N-methyl-D-aspartic acid receptor antagonist (memantine) are symptomatic but poorly affect the progression of the disease. In recent decades, the concept of amyloid-β (Aβ) cascade and tau hyperphosphorylation leading to AD has dominated AD drug development. However, pharmacotherapies targeting Aβ and tau have limited success. It is generally believed that AD is caused by multiple pathological processes resulting from Aβ abnormality, tau phosphorylation, neuroinflammation, neurotransmitter dysregulation, and oxidative stress. In this review we updated the recent development of new therapeutics that regulate neurotransmitters, inflammation, lipid metabolism, autophagy, microbiota, circadian rhythm, and disease-modified genes for AD in preclinical research and clinical trials. It is to emphasize the importance of early diagnosis and multiple-target intervention, which may provide a promising outcome for AD treatment.
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“The majority of phase II and III trials center around neurotransmitter receptors and Aβ mechanisms, while tau and inflammation drugs are more prominent in phase II, often featuring repurposed compounds.”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [437]
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“The major mechanisms of action center around: 1) neurotransmitter receptors, including AChE, NMDA receptor, 5-hydroxytryptamine receptor, nicotinic α7 receptor, and adrenoceptor; 2) Aβ, including the reduction of Aβ production (such as γ-secretase inhibitors and modulators, BACE1 inhibitors, and α-secretase activators), prevention of Aβ aggregation, and enhancing Aβ clearance (vaccines and ant”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [437]
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Metadata
- Authors
- Zhang, F., Zhong, R.-J., Cheng, C., Li, S., & Le, W.-D.
- Affiliations
- Dalian Medical University (CN)
- Venue
- Acta Pharmacologica Sinica
- Published
- 2020-12-02
- Volume
- 42
- Issue
- 9
- Pages
- 1382-1389
- ISSN
- 0253-9756 (ISSN-L)
- 1671-4083
- 1745-7254
- PMC
- PMC8379190
- OpenAlex
- W3106951507
- Cited by
- 105
- References
- 118
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 21 · 2023: 32 · 2022: 15 · 2021: 12
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Pharmacologica Sinica (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81771521)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, tau hyperphosphorylation, disease-modifying therapy, neuroinflammation, neurotransmitter dysregulation, oxidative stress, lipid metabolism, autophagy, gut microbiota, circadian rhythm, early diagnosis, cholinesterase inhibitors, memantine, preclinical drug development
- MeSH terms
- Neuroinflammatory Diseases, Aged, Alzheimer Disease, Cholinesterase Inhibitors, Humans, Phosphorylation, Amyloid beta-Peptides, tau Proteins, Neurodegenerative Diseases
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