Article
Biochemistry & Molecular Biology
Shoaib Manzoor, Moustafa T. Gabr, Bisma Rasool, Kavita Pal, Nasimul Hoda
Summary: The study reported a new series of deoxyvasicinone analogues as dual inhibitors of acetylcholinesterase (AChE) and tau aggregation, demonstrating their potential as multitargeted ligands for Alzheimer's disease. Among the synthesized compounds, one particular compound showed significant inhibition of AChE activity and cellular tau oligomerization, highlighting its promising potential for anti-AD drug development.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Huiqin Zhang, Wei Wei, Ming Zhao, Lina Ma, Xuefan Jiang, Hui Pei, Yu Cao, Hao Li
Summary: Extracellular neuritic plaques and intracellular neurofibrillary tangles, composed of amyloid-beta and phosphorylated tau protein respectively, are hallmark proteins of Alzheimer's disease. The interactions between these proteins have been extensively studied, with A beta accelerating tau phosphorylation, tau mediating A beta toxicity, and potential synergistic effects on microglial cells and astrocytes. Understanding these interactions may lead to new interventions against Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Mohammad Rafi Khezri, Keyvan Yousefi, Negin Mahboubi, Darya Hodaei, Morteza Ghasemnejad-Berenji
Summary: Alzheimer's disease (AD) is a common neurodegenerative disorder worldwide, and its association with diseases like diabetes has been well-studied. Metformin, a medication commonly used for type 2 diabetes, has shown potential disease-modifying effects on various aspects of AD pathophysiology.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Jian Li, Chaojie Zheng, Qi Ge, Shaozhen Yan, Manish D. Paranjpe, Shuo Hu, Yun Zhou
Summary: This study found an association between long-term donepezil treatment and increased brain neuropathological burden and worsened cognitive performance in MCI patients, suggesting potential negative effects of treatment on amyloid and tau burden as well as cognitive function. The importance of using noninvasive and quantitative PET imaging techniques to elucidate the consequences of drug treatment in AD studies is highlighted.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Ly Thi Huong Luu Le, Jeeyoung Lee, Dongjoon Im, Sunha Park, Kyoung-Doo Hwang, Jung Hoon Lee, Yanxialei Jiang, Yong-Seok Lee, Young Ho Suh, Hugh I. Kim, Min Jae Lee
Summary: In tauopathy conditions, tau protein aggregates into insoluble filaments, contributing to the pathology of Alzheimer's disease. This study demonstrates that a specific region of tau, called tau AD nucleation core (tau-AC), is responsible for initiating self-aggregation of tau and recruiting full-length tau to form filaments. Phosphorylation of tau-AC reduces its ability to oligomerize and seed tau aggregation. Importantly, the presence of tau-AC species impairs neuronal function and memory retrieval, highlighting its significance as a therapeutic target for Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Xueling Yuan, Zhuo Wang, Lei Zhang, Rubo Sui, Suliman Khan
Summary: Liquiritigenin was found to be an efficient inhibitor of tau amyloid fibril formation, reducing ROS and caspase-3 activity, and increasing CAT activity to alleviate neurotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Ashim Paul, Guru KrishnaKumar Viswanathan, Adi Huber, Elad Arad, Hamutal Engel, Raz Jelinek, Ehud Gazit, Daniel Segal
Summary: The dopamine-based hybrid molecule NQDA effectively inhibits the aggregation of key tau-derived amyloidogenic fragments PHF6 and PHF6*, as well as full-length tau protein, in in vitro experiments. It disassembles preformed fibrils and demonstrates significant binding efficiency with tau fibrils through entropic and enthalpic processes. NQDA shows comparable or lower IC50 values for inhibiting fibril formation compared to other amyloid inhibitors, suggesting its potential as a scaffold for developing therapeutics for Alzheimer's disease and other tauopathies.
Article
Chemistry, Physical
Sepideh Najar-Ahmadi, Hossein Haghaei, Safar Farajnia, Reza Yekta, Jafar Ezzati Nazhad Dolatabadi, Mohammad-Reza Rashidi
Summary: Alzheimer's disease is characterized by the accumulation of beta amyloid fibrils and phosphorylated tau in neurofibrillary tangles. Research suggests that donepezil may interact with tau protein, enhancing its binding to the protein with the main forces involved being van der Waals and hydrogen bonding. Molecular modeling analysis shows that donepezil binds to a cavity on the R2 region-microtubule binding domain of tau monomer.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Clinical Neurology
Yalun Zhang, Yi Zhang, Yahyah Aman, Cheung Toa Ng, Wing-Hin Chau, Zhigang Zhang, Ming Yue, Christopher Bohm, Yizhen Jia, Siwen Li, Qiuju Yuan, Jennifer Griffin, Kin Chiu, Dana S. M. Wong, Binbin Wang, Dongyan Jin, Ekaterina Rogaeva, Paul E. Fraser, Evandro F. Fang, Peter St George-Hyslop, You-Qiang Song
Summary: Research has shown that the transcription factor PAX6 is increased in Alzheimer's disease, playing a key role in the hyperphosphorylation of tau protein induced by amyloid-beta. Downregulation of PAX6 can protect against amyloid-beta-induced neuronal death. This study provides novel potential targets for pharmaceutical intervention by modulating signaling pathways involving CDK/pRB/E2F1.
Article
Plant Sciences
Caixia Zang, Hui Liu, Junmei Shang, Hanyu Yang, Lu Wang, Chanjuan Sheng, Zihong Zhang, Xiuqi Bao, Yang Yu, Xinsheng Yao, Dan Zhang
Summary: The study demonstrates that GJ-4 improves cognitive deficits in APP/PS1 transgenic mice by reducing A beta levels, inhibiting tau protein phosphorylation, and suppressing neuroinflammatory responses. These findings provide a basis for further development of GJ-4 as a potential treatment for AD.
Article
Chemistry, Medicinal
Xinnan Li, Tiantian Li, Pengfei Zhang, Xinuo Li, Li Lu, Yuan Sun, Bocheng Zhang, Stephanie Allen, Lisa White, James Phillips, Zheying Zhu, Hequan Yao, Jinyi Xu
Summary: Novel compounds have been discovered for the potential treatment of Alzheimer's disease (AD) using a multitarget strategy. These compounds showed significant inhibitory activity against acetylcholinesterase (AChE) and demonstrated various beneficial pharmacological activities in vitro and in vivo, including antioxidant, neuroprotective, and anti-Tau phosphorylation effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Hee-Jeong Choi, Jin-Hee Park, Yoo Joo Jeong, Jeong-Woo Hwang, Soojung Lee, Heeyong Lee, Eunyoung Seol, Ik-whi Kim, Byung-Yoon Cha, Jinsoo Seo, Minho Moon, Hyang-Sook Hoe
Summary: The study found that intraperitoneal injection of donepezil can reduce the number of Aβ plaques in the brain and decrease glial cell activation in 5xFAD mice. However, it has little effect on tau pathology.
Article
Biochemistry & Molecular Biology
Prabhat Tiwari, Nicholas S. Tolwinski
Summary: A dementia case is diagnosed every three seconds worldwide, with 50-60% of cases being caused by Alzheimer's disease (AD). The deposition of amyloid beta (Aβ) is believed to be correlated with the onset of dementia, although it remains unclear whether Aβ is causative. Optogenetic techniques provide a precise way to regulate cellular dynamics and could offer a better understanding of the etiology of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Daniela Malafaia, Helio M. T. Albuquerque, Artur M. S. Silva
Summary: Alzheimer's disease is a common form of dementia in the elderly with no cure currently available. Multi-target compounds show promise in addressing various factors related to AD. Accumulation of Aβ plaques and NFTs are key features of AD, attracting significant research attention for early diagnosis and treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Clinical Neurology
Ziqi Fan, Zheyu Li, Shuai Zhao, Yanxing Chen, Yujie Su, Guoping Peng, Benyan Luo
Summary: This study conducted a meta-analysis on salivary biomarkers in Alzheimer's disease (AD) and found that salivary β-amyloid 1-42 (Aβ(1-42)) showed higher sensitivity in early AD diagnosis. However, larger studies are needed to confirm the sensitivity and specificity of salivary Aβ(1-42) in AD diagnosis.
JOURNAL OF NEUROLOGY
(2023)