Current study on diagnosis and treatment of Alzheimer’s disease by targeting amyloid b-protein

Hua, Kai-Ye; Zhao, Wei‐Jiang

doi:10.5114/fn.2022.119778

Cited by 4 publications

(1 citation statement)

References 67 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Progressive cognitive impairment is one of the main symptoms of AD patients. In recent years, many potential reagents to improve AD symptoms have been studied, but about 99.6% of them fail in clinical trials [6][7][8][9][10]. Therefore, it is urgent to develop new effective approaches to treat AD.…”

Section: Introductionmentioning

confidence: 99%

Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer’s Disease through NAD+/SIRT1-Mediated Autophagy

Yang,

Zhou,

Zhao

et al. 2023

Antioxidants

View full text Add to dashboard Cite

To date, Alzheimer’s disease (AD) has grown to be a predominant health challenge that disturbs the elderly population. Studies have shown that mitochondrial dysfunction is one of the most significant features of AD. Transplantation therapy of healthy mitochondria (mitotherapy), as a novel therapeutic strategy to restore mitochondrial function, is proposed to treat the mitochondria−associated disease. Also, the molecular mechanism of mitotherapy remains unclear. Here, we applied the mitotherapy in AD model mice induced by amyloid−β (Aβ) plaque deposition and suggested that autophagy would be an important mechanism of the mitotherapy. After the healthy mitochondria entered the defective neuronal cells damaged by the misfolded Aβ protein, autophagy was activated through the NAD+−dependent deacetylase sirtuin 1 (SIRT1) signal. The damaged mitochondria and Aβ protein were eliminated by autophagy, which could also decrease the content of radical oxygen species (ROS). Moreover, the levels of brain−derived neurotrophic factor (BDNF) and extracellular−regulated protein kinases (ERK) phosphorylation increased after mitotherapy, which would be beneficial to repair neuronal function. As a result, the cognitive ability of AD animals was ameliorated in a water maze test after the healthy mitochondria were administrated to the mice. The study indicated that mitotherapy would be an effective approach to AD treatment through the mechanism of autophagy activation.

show abstract

Section: Introductionmentioning

confidence: 99%

Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer’s Disease through NAD+/SIRT1-Mediated Autophagy

Yang,

Zhou,

Zhao

et al. 2023

Antioxidants

View full text Add to dashboard Cite

show abstract

Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants

Du,

Wei,

Guo

et al. 2024

Med Chem Res

View full text Add to dashboard Cite

Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants

Du,

Wei,

Guo

et al. 2024

Preprint

View full text Add to dashboard Cite

A series of 8-(piperazin-1-yl)imidazo[1,2-a]pyrazine derivatives were designed and synthesized as acetylcholinesterase inhibitors (AChEIs) and antioxidants for the treatment of Alzheimer's disease (AD). Moreover, the biological evaluation results demonstrated that these synthesized compounds exhibited moderate inhibitory activities toward acetylcholinesterase (AChE) and radical scavenging activities. Among them, compound 14r was the most potent AChE inhibitor with an IC50 value of 0.47 µM and moderate inhibitory activity against butyrylcholinesterase (BuChE) (IC50 = 11.02 µM). Meanwhile compound 14r had the best selectivity of AChE and selectivity index (SI) values was 23.45. Compound 14r has better activity as well as AChE selectivity compared to reference drug galantamine (AChE IC50 = 5.01 µM, BuChE IC50 = 18.46 µM, SI = 3.68). Compound 14o had the best antioxidant activity with an IC50 value of 89.33 µM, which was lower than that of ascorbic acid (IC50 value = 25.70 µM) as the control drug. Furthermore, the results of molecular docking studies indicated that 14r could simultaneously bind to both catalytic active site and peripheral anionic site of AChE, which was consistent with the mixed inhibition pattern shown by enzyme kinetic studies. The interaction’s stability of 14r-AChE/BuChE were also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 14r in the cavity of the AChE. In addition, the molecular properties of all compounds were predicted online through the SwissADME, and the best active compound 14r matched the properties of most orally administered drugs. Based on the biological activity and molecular properties, compound 14r as AChEI was valuable for further development.

show abstract

Current study on diagnosis and treatment of Alzheimer’s disease by targeting amyloid b-protein

Cited by 4 publications

References 67 publications

Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer’s Disease through NAD+/SIRT1-Mediated Autophagy

Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer’s Disease through NAD+/SIRT1-Mediated Autophagy

Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants

Design, synthesis and evaluation of imidazo[1,2-a]pyrazin-8(7H)-one derivatives as acetylcholinesterase inhibitors and antioxidants

Contact Info

Product

Resources

About