Article
Chemistry, Medicinal
Li-Cheng Zhou, Ying-Fan Liang, Yi Huang, Gui-Xiang Yang, Lu-Lu Zheng, Jia-Min Sun, Yang Li, Fu-Li Zhu, He-Wen Qian, Rui Wang, Lei Ma
Summary: The study developed diosgenin-indole compounds with potential neuroprotective effects against H2O2, 6-OHDA, and Aβ damages. Compound 5b showed promising results with strong binding affinity to Aβ(1-42), favorable BBB permeation, and absorption abilities. In vivo experiments demonstrated that 5b attenuated memory and learning impairments of Aβ-injected mice, suggesting its potential as a dual-functional neuroprotective agent against AD.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shagufta Parveen, Aneeqa Batool, Nusrat Shafiq, Maryam Rashid, Ayesha Sultan, Gezahign Fentahun Wondmie, Yousef A. Bin Jardan, Simone Brogi, Mohammed Bourhia
Summary: In this study, compounds with antioxidant activity were screened from pomegranate peels for the treatment of Alzheimer's disease. The inhibitory effect of estrogen on Alzheimer's disease and its role in protecting the brain were investigated. Computational calculations and experiments identified hesperidin as a potential candidate for drug discovery.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yi Wang, Kaiyue Wang, Junyuan Yan, Qian Zhou, Xiaoying Wang
Summary: Alzheimer's disease is an incurable type of dementia in the elderly, and our understanding of its etiology and pathogenesis is limited. However, several hypotheses related to risk factors have been proposed, and plant-derived dietary polyphenols have been shown to have protective effects against neurodegenerative diseases. This review summarizes the regulatory effects of these polyphenols on AD-related molecular mechanisms and discusses the issue of bioavailability and potential improvements, aiming to encourage further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Bikash R. Sahoo, Pritam Kumar Panda, Wenguang Liang, Wei-Jen Tang, Rajeev Ahuja, Ayyalusamy Ramamoorthy
Summary: The study demonstrates that cf-E111Q-IDE degrades Aβ(1-40) through a non-chaperone mechanism with reduced impact on aggregation kinetics. Zinc binding to Aβ(1-40) inactivates cf-E111Q-IDE's catalytic function, while zinc removal restores its function. These findings highlight the catalytic role of cf-E111Q-IDE in Aβ degradation and suggest the development of zinc chelators as a therapeutic strategy to modulate IDE's function.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Victor Valverde-Salazar, Daniel Ruiz-Gabarre, Vega Garcia-Escudero
Summary: Alzheimer's disease (AD) is a common form of dementia characterized by memory decline, cognitive impairment, and several pathological changes in the brain. Oxidative stress and inflammation play important roles in the development of AD. Green tea and its active compound EGCG have shown potential therapeutic effects in modulating AD through their antioxidative and anti-inflammatory properties. EGCG can regulate inflammatory processes, reduce protein aggregation, and promote neuronal survival pathways, making it a suitable candidate for the treatment of neurodegenerative disorders involving oxidative stress and inflammation.
Article
Plant Sciences
Antonis Ververis, Kristia Ioannou, Sotiris Kyriakou, Niki Violaki, Mihalis I. Panayiotidis, Michael Plioukas, Kyproula Christodoulou
Summary: Alzheimer's disease (AD) is a prevalent neurodegenerative condition in aging populations with no effective therapy available. Recent research has focused on reducing the toxic amyloid beta aggregates and oxidative stress, which are closely associated with AD. Medicinal plants, such as Sideritis scardica (SS), have shown neuroprotective effects against AD. We investigated the antioxidant and neuroprotective potential of eight solvent fractions derived from SS and found that most fractions were rich in phenolics and flavonoids, with significant antioxidant activity. Four SS extracts were able to partially restore cell viability in A beta(25-35)-treated neuroblastoma cells, indicating their neuroprotective properties. These extracts contained neuroprotective substances like apigenin, myricetin-3-galactoside, and ellagic acid. The findings suggest that specific SS mixtures have potential for the development of herbal drugs and functional food products to alleviate AD symptoms.
Review
Biochemistry & Molecular Biology
Anne-Cathrine S. Vogt, Gary T. Jennings, Mona O. Mohsen, Monique Vogel, Martin F. Bachmann
Summary: Alzheimer's disease is the most common form of dementia and is responsible for 60-70% of cases. The number of people with dementia is expected to triple by 2050 due to an aging population. Currently, there are only symptomatic treatments available, making it crucial to develop novel therapeutic strategies to prevent or delay the onset of Alzheimer's disease. This mini-review focuses on the understanding of Alzheimer's disease pathobiology and discusses current immunomodulating therapies targeting amyloid-beta protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Asra Nasir Khan, Kundlik Gadhave, Mohammad Furkan, Prateek Kumar, Mohammad Khursheed Siddiqi, Rajanish Giri, Rizwan Hasan Khan
Summary: Thionamide antibiotics prothionamide and ethionamide could effectively inhibit amyloid formation of human insulin and A beta 42, and protect neuroblastoma cells from the toxic effects of amyloids. These drugs exert their anti-amyloid potency by stabilizing proteins in their native state and also possess antioxidant properties.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Review
Chemistry, Medicinal
Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Summary: Alzheimer's disease (AD) is a difficult to treat progressive neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) plaques in the brain. A beta interacts with various receptors on the plasma membrane and mediates signaling pathways that contribute to the development of AD. Despite ongoing research, there are currently no effective medications for AD. This review discusses the importance of A beta in the pathogenesis of AD, recent progress in targeting A beta-related receptors and compounds, and the challenges and opportunities in developing effective therapies for AD.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Liyuan Tao, Miaoyang Hu, Xiaobao Zhang, Xi Wang, Yujuan Zhang, Xufeng Chen, Jinrong Tang, Jun Wang
Summary: This study revealed that Meth significantly impacted the ingestion and accumulation of Aβ(42) in microglia and led to impaired degradation of Aβ, promoting Aβ(42) spreading through the exosomal pathway.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Akiko Amano, Nobuo Sanjo, Wataru Araki, Yasutaka Anraku, Makoto Nakakido, Etsuro Matsubara, Takami Tomiyama, Tetsuya Nagata, Kouhei Tsumoto, Kazunori Kataoka, Takanori Yokota
Summary: Researchers developed polymeric nanomicelles capable of passing through the blood-brain barrier to deliver specific antibodies to the brain. The administration of 6H4 antibody fragments in polymeric nanomicelles for 10 weeks significantly reduced the amounts of toxic A beta species in the brain and inhibited the formation of A beta plaques. Behavioral analysis also showed an improvement in spatial reference memory in mice with Alzheimer's disease.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Elena Tamagno, Michela Guglielmotto, Valeria Vasciaveo, Massimo Tabaton
Summary: The pathogenesis of Alzheimer's disease involves the accumulation of beta amyloid and vulnerability of the brain to oxidative stress, which are linked to each other. It is difficult to determine which comes first, Aβ or oxidative stress. Evidence suggests that oxidative stress occurs early in the development of Alzheimer's disease and plays a crucial role in the manifestation of clinical and pathological symptoms.
Article
Biochemistry & Molecular Biology
Willy Smeralda, Marc Since, Julien Cardin, Sophie Corvaisier, Sophie Lecomte, Christophe Cullin, Aurelie Malzert-Freon
Summary: The study focused on the molecular interactions between the amyloid beta peptide associated with Alzheimer's disease and biological membranes, developing simple liposomal formulations mimicking neuronal cell membranes. Characterization of interactions through a multiparametric procedure laid the methodological foundation for developing an original model describing interactions between A beta peptide and lipids.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Cell Biology
Marva Lachish, Nina Fainstein, Tal Ganz, Lihi Sofer, Tamir Ben-Hur
Summary: Brain neural precursor cells (NPCs) support microglial function to clear excess amyloid beta (Aβ), but NPC from the Alzheimer's disease (AD) environment fail to do so, potentially accelerating disease pathology.
Review
Biochemistry & Molecular Biology
Lucia Gallego Villarejo, Lisa Bachmann, David Marks, Maite Brachthaeuser, Alexander Geidies, Thorsten Mueller
Summary: Intracellular amyloid beta (iAβ) plays a crucial role in neurodegeneration and serves as a pathological marker. Modulating iAβ through pharmacological treatment has shown beneficial effects on cognitive properties. Future research should focus on the impact of viral infections on iAβ generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Angela Jeong, Kiall Francis Suazo, W. Gibson Wood, Mark D. Distefano, Ling Li
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2018)
Article
Hematology
Jianming Wu, Yunfang Li, Randy M. Schuller, Ling Li, Anne-Sophie Litmeyer, Gregor Bein, Ulrich Sachs, Behnaz Bayat
Article
Pharmacology & Pharmacy
Andrew L. Zhou, Suresh K. Swaminathan, Geoffry L. Curran, Joseph F. Poduslo, Val J. Lowe, Ling Li, Karunya K. Kandimalla
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Review
Cell & Tissue Engineering
Andrew T. Crane, Rajagopal N. Aravalli, Atsushi Asakura, Andrew W. Grande, Venkatramana D. Krishna, Daniel F. Carlson, Maxim C-J Cheeran, Georgette Danczyk, James R. Dutton, Perry B. Hackett, Wei-Shou Hu, Ling Li, Wei-Cheng Lu, Zachary D. Miller, Timothy D. O'Brien, Angela Panoskaltsis-Mortari, Ann M. Parr, Clairice Pearce, Mercedes Ruiz-Estevez, Maple Shiao, Christopher J. Sipe, Nikolas G. Toman, Joseph Voth, Hui Xie, Clifford J. Steer, Walter C. Low
CELL TRANSPLANTATION
(2019)
Review
Neurosciences
Dustin Chernick, Stephanie Ortiz-Valle, Angela Jeong, Wenhui Qu, Ling Li
NEUROSCIENCE LETTERS
(2019)
Article
Neurosciences
Wenhui Qu, Kiall F. Suazo, Wenfeng Liu, Shaowu Cheng, Angela Jeong, David Hottman, Li-Lian Yuan, Mark D. Distefano, Ling Li
Summary: Protein prenylation is crucial for regulating cellular signaling pathways, with FT and GGT enzymes playing essential roles in the process. FT haplodeficiency rescues cognitive function in Alzheimer's disease models, whereas GGT deficiency leads to synaptic and cognitive deficits. A novel prenylomic analysis identifies distinct pools of prenylated proteins affected by specific knockout of FT and GGT in forebrain neurons, indicating their essential roles in synaptic and cognitive functions.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dustin Chernick, Rui Zhong, Ling Li
Article
Multidisciplinary Sciences
Kiall F. Suazo, Angela Jeong, Mina Ahmadi, Caroline Brown, Wenhui Qu, Ling Li, Mark D. Distefano
Summary: Protein prenylation is crucial for signal transduction processes, and using the probe C15AlkOPP, this study explored metabolic labeling and identification of prenylated proteins in various cell lines. The research identified common prenylated proteins in three brain-related cell lines and also unique prenylated proteins in each type. Additionally, inhibition of farnesylation in primary astrocytes showed different responses of farnesylated proteins to an FTI, suggesting the potential utility of this chemical proteomic approach in studying prenylated proteins in different diseases.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Yue-Xuan Li, Yushuang Wei, Rui Zhong, Ling Li, Hong-Bo Pang
Summary: Studies have shown that TP peptide can facilitate cellular uptake of various NPs through a bystander manner, providing a new delivery strategy without the need for chemical modifications.
Review
Clinical Neurology
Wenhui Qu, Ling Li
Summary: Microglia, the resident immune cells in the brain, play crucial roles in regulating neuronal function. The triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial function. It orchestrates microglial transcriptome programming, affecting their chemotaxis, phagocytosis, and inflammatory responses, as well as their regulation of synaptic function in health and disease. Understanding the role of TREM2 in physiological conditions and Alzheimer's disease (AD) is of rapidly growing interest.
Article
Neurosciences
Angela Jeong, Shaowu Cheng, Rui Zhong, David A. Bennett, Martin O. Bergo, Ling Li
Summary: This study found that levels of FT and membrane-associated H-Ras were increased in individuals with AD and MCI compared to those with no cognitive impairment. Deleting neuronal FT mitigated memory impairment and amyloid neuropathology in transgenic AD model mice by suppressing amyloid generation and reversing hyperactivation of mTORC1 signaling. Targeting FT or its downstream signaling pathways could be a potential therapeutic strategy against AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Angela Jeong, Shelby A. Auger, Sanjay Maity, Kristina Fredriksen, Rui Zhong, Ling Li, Mark D. Distefano
Summary: Dysregulation of protein prenylation is associated with various diseases, including Alzheimer's disease. Using a combination of metabolic labeling and proteomic analysis, 36 prenylated proteins were identified in the brains of transgenic AD mice. Importantly, the prenylated forms of 15 proteins were consistently upregulated in AD mice compared to wild-type controls. This in vivo metabolic labeling approach has the potential to identify therapeutic targets for refractory diseases and can be applied to other types of protein modifications.
ACS CHEMICAL BIOLOGY
(2022)
Article
Neurosciences
Wenhui Qu, Angela Jeong, Rui Zhong, Josslen S. Thieschafer, Andrea Gram, Ling Li
Summary: Alzheimer's disease is a fatal neurodegenerative disorder with no cure. Recent evidence suggests that the small GTPase H-Ras may modulate the pathogenic process of AD and hold potential as a therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kiall F. Suazo, Jakub Belicek, Garrett L. Schey, Shelby A. Auger, Alexandru M. Petre, Ling Li, Katarzyna M. Blazewska, David Kopecny, Mark D. Distefano
Summary: This study discusses the discovery of a non-canonical protein prenylation modification on ALDH9A1 and suggests that it may originate from endogenous farnesal or geranygeranial. This reversible prenoyl modification expands the current understanding of protein prenylation and may serve as a new mechanism for controlling enzyme function.
RSC CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Wenhui Qu, Ling Li
JOURNAL OF NEUROSCIENCE
(2020)