TY - JOUR
T1 - New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease
AU - Zhang, Feng
AU - Zhong, Ru jia
AU - Cheng, Cheng
AU - Li, Song
AU - Le, Wei dong
N1 - Funding Information:
This work was supported by the funding from National Natural Science Foundation of China (NSFC 81771521).
Publisher Copyright:
© 2020, CPS and SIMM.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - anti-inflammatory drugs
KW - autophagic modifiers
KW - circadian rhythm regulators
KW - gene and cell therapies
KW - gut microbiota regulators
KW - lipid metabolism regulators
KW - new therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85097089264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097089264&partnerID=8YFLogxK
U2 - 10.1038/s41401-020-00565-5
DO - 10.1038/s41401-020-00565-5
M3 - Review article
C2 - 33268824
AN - SCOPUS:85097089264
SN - 1671-4083
VL - 42
SP - 1382
EP - 1389
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
IS - 9
ER -