Article
Biochemistry & Molecular Biology
Anqesha Murray, Lufeng Yan, James M. Gibson, Jian Liu, David Eliezer, Guy Lippens, Fuming Zhang, Robert J. Linhardt, Jing Zhao, Chunyu Wang
Summary: This study investigated the interaction between tau and heparan sulfate (HS) using NMR. The results revealed that PRR2 is a crucial domain for the interaction between tau and HS.
Article
Cell Biology
Veronica Mutti, Giulia Carini, Alice Filippini, Stefania Castrezzati, Lorena Giugno, Massimo Gennarelli, Isabella Russo
Summary: Chronic neuroinflammation is a crucial factor in the progression of neurodegenerative diseases like Parkinson's and Alzheimer's. The gene LRRK2, which is mutated in these diseases, has been identified as a key mediator of neuroinflammation. This study further validated LRRK2 kinase inhibition as a potential therapeutic intervention for neuroinflammation in preclinical models of Alzheimer's and Parkinson's.
Article
Clinical Neurology
Limin Yin, Jianhui Zhou, Tianyou Li, Xinghua Wang, Wenlong Xue, Jie Zhang, Lingxi Lin, Ning Wang, Xinyi Kang, Yu Zhou, Hong Liu, Yang Li
Summary: A novel regulator, the DAT-CDK9-TFEB signaling axis, has been identified to play a crucial role in lysosome biogenesis. The study sheds light on the mechanisms of protein quality control under pathophysiological conditions.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Zongyang Li, Xiangbao Meng, Guoxu Ma, Wenlan Liu, Weiping Li, Qian Cai, Sicen Wang, Guodong Huang, Yuan Zhang
Summary: In this study, LPD was identified as a novel PPAR gamma agonist with neuroprotective effects in Alzheimer's disease models. LPD treatment reduced levels of A beta plaques and improved cognitive deficits through PPAR gamma-dependent enhancement of mitophagy. Additionally, the protective effects of LPD were reversed by a PPAR gamma antagonist.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Chemistry, Medicinal
Tingkai Chen, Shenghu Sang, Yuqing Wei, Yujie Ge, Jisheng Jin, Yaoyao Bian, Yuqiong Pei, Nianguang Li, Haopeng Sun, Yao Chen
Summary: A series of tetrahydrothienopyridine derivatives were designed, synthesized, and evaluated as selective BChE inhibitors. The compounds were analyzed using HRMS, 1H NMR, and 13C NMR. The most potent and selective inhibitor against BChE was found to be 6n.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Clinical Neurology
Glen Wunderlich, Zuzana Blahova, Miguel Garcia, Frank Jessen
Summary: This study assessed the efficacy and safety of BI 425809 in treating cognitive impairment associated with probable Alzheimer's disease dementia. The results showed that BI 425809 did not lead to clinically meaningful changes from baseline in patients with mild-to-moderate probable Alzheimer's disease dementia.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Shuaishuai Xing, Ying Chen, Baichen Xiong, Weixuan Lu, Qi Li, Yuanyuan Wang, Mengxia Jiao, Feng Feng, Yao Chen, Wenyuan Liu, Haopeng Sun
Summary: 2513-4169, a promising lead compound, shows potential inhibitory activity and neuroprotective effect for treating Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Engineering, Environmental
Dongsheng Zhao, Jiyu Song, Yiwen Zhang, Zhiquan Lin, Bo He, Nanfu Qiao, Kangping Huang, Wei Zhang, Shuang Ge, Yuying Li, B. Larry Li, Kang Xie, Guicai Liu
Summary: Polyamide (PA) films were synthesized under different posttreatment methods to investigate the relationship between film structure and membrane performance. The combined posttreatment method of hexane activation and water curing significantly increased membrane permeability and selectivity. The increased pore size, enhanced hydrophilicity, reduced thickness and crosslinking degree of the PA film, as well as the increased electrostatic repulsion between carboxyl groups and divalent anions, contributed to the improved performance.
JOURNAL OF WATER PROCESS ENGINEERING
(2023)
Review
Neurosciences
Ammara Shaikh, Fairus Ahmad, Seong Lin Teoh, Jaya Kumar, Mohamad Fairuz Yahaya
Summary: Alzheimer's disease is characterized by the pathological accumulation of amyloid and neurofibrillary tangles in the brain, leading to neuronal damage and impaired synapses, resulting in cognitive and behavioral abnormalities. Dysfunction in multiple neurotransmitter systems, including the dopaminergic system, contributes to the functional deficits. The dopaminergic system plays a crucial role in modulating movement, cognition, and behavior, making it a promising target for addressing movement and cognitive deficits in AD. Recent research has shown that the dopamine transporter, previously overlooked, is a potential target for enhancing cognition and addressing dopaminergic dysfunction in AD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Jin-Ying Liu, Hong-Yan Guo, Zhe-Shan Quan, Qing-Kun Shen, Hong Cui, Xiaoting Li
Summary: Alzheimer's disease (AD), a persistent neurological dysfunction, is increasingly common with aging and poses a serious threat to the health of the elderly. Despite the lack of effective treatment for AD, researchers continue to explore its pathogenesis and potential therapeutic drugs. Natural products have gained attention due to their unique advantages, as one molecule can interact with multiple AD-related targets, making them potential candidates for multi-target drugs. Natural products and their derivatives that can alleviate pathological changes in AD should be intensively studied. This review focuses on research on natural products and their derivatives for the treatment of AD.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pavel Panteleev, Victoria N. Safronova, Roman N. Kruglikov, Ilia A. Bolosov, Ivan Bogdanov, Tatiana Ovchinnikova
Summary: In recent years, an increasing number of bacteria have developed resistance to antibiotics. This study discovered a novel family of proline-rich cathelicidins, called Bac7-like, from the genomes of camelid species. These peptides showed potent antimicrobial activity by inhibiting bacterial protein synthesis and effectively penetrating bacterial membranes, while having minimal toxicity to mammalian cells. The study also found that these peptides did not induce bacterial resistance and exhibited both pro- and anti-inflammatory effects on human cells. The pronounced antibacterial activity and moderate adverse effects of these peptides make them promising candidates for developing peptide antibiotics.
Review
Neurosciences
Oliver W. G. Wood, Jason H. Y. Yeung, Richard L. M. Faull, Andrea Kwakowsky
Summary: Glutamate, as the main excitatory neurotransmitter in the human central nervous system, plays a crucial role in normal physiological processes. Dysregulation of the glutamatergic system, especially the expression of the excitatory amino acid transporter 2 (EAAT2), can have significant implications in acute brain injury and neurodegenerative diseases. This systematic review identified 29 articles that examined EAAT2 expression in the AD human brain or used human-derived cell cultures. While the findings were inconclusive regarding EAAT2 regulation in AD, changes in localization and correlation with symptomatology were observed. These findings suggest that EAAT2 alterations may play a key role in AD progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Joanna E. Luo, Yue-Ming Li
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with the accumulation of A beta peptides. γ-secretase, the enzyme responsible for generating A beta peptides, has been a challenging drug target due to its complex structure and function. However, the development of γ-secretase modulators has opened up new possibilities for Alzheimer's disease treatment.
CELL AND BIOSCIENCE
(2022)
Article
Medicine, Research & Experimental
Sanjay Arora, Buddhadev Layek, Jagdish Singh
Summary: This study demonstrated efficient brain-targeted delivery of ApoE2 gene therapy using surface-modified liposomes, with significantly higher ApoE2 expression in neurons and potential for effective AD treatment.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Physical
Zhipeng Zhang, Maojun Cheng, Jie Guo, Yang Wan, Rikang Wang, Yuanying Fang, Yi Jin, Sai-Sai Xie, Jing Liu
Summary: The pyrazolone structure was found to be a promising pharmacophore targeting BuChE in this study. Compound 5i showed the highest selective BuChE inhibitory activity and demonstrated good abilities to penetrate the blood-brain barrier and scavenge free radicals, making it a promising lead compound for further investigation in the treatment of Alzheimer's disease.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)