Review
Chemistry, Applied
Zhiyuan Zhang, Shuai Wang, Haining Tan, Pei Yang, Yuanyuan Li, Lingchuan Xu, Baoguo Duan, Yuhong Liu
Summary: This paper reviews recent research on the regulation of natural polysaccharides in Alzheimer's disease (AD) and systematically lists possible intervention pathways of polysaccharides targeting different mechanisms.
CARBOHYDRATE POLYMERS
(2022)
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)
Article
Geriatrics & Gerontology
Chan Liu, Zhipei Sang, Hong Pan, Qin Wu, Yu Qiu, Jingshan Shi
Summary: The study synthesized a novel multi-target-directed ligand (AP5) and used computational simulations and in vivo pharmacokinetic evaluations to confirm its potential. The results showed that AP5 can simultaneously bind to the peripheral and catalytic sites of AChE and has desirable pharmacokinetic characteristics and drug-likeness. AP5 can inhibit AChE activity and AChE-induced Aβ aggregation, reduce Aβ plaque deposition, suppress inflammation, and prevent neuronal and synaptic damage in Alzheimer's disease models.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Benita Wiatrak, Paulina Jawien, Agnieszka Matuszewska, Adam Szelag, Adriana Kubis-Kubiak
Summary: This study aimed to investigate the impact of amyloid fragments on oxidative stress and found that amyloid fragments have antioxidant properties, protecting neurons from neuroinflammation-induced damage. Among the tested fragments, the 1-40 fragment showed a stronger antioxidant effect.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Vivek Kumar Sharma, Thakur Gurjeet Singh, Shareen Singh, Nikhil Garg, Sonia Dhiman
Summary: Apoptosis is a crucial biochemical process that regulates cell survival and disease progression, particularly in neurodegenerative disorders like Alzheimer's disease. Dysregulated apoptosis can lead to neuronal loss and is a key factor in the pathological progression of the disease. Identifying potential targets related to apoptosis may be valuable in developing therapeutics for Alzheimer's disease.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, Isabella Russo
Summary: The accumulation of amyloid-beta in Alzheimer's disease (AD) brains causes reactive astrogliosis and neuroinflammatory response. This study investigates the role of leucine-rich repeat kinase 2 (LRRK2) in regulating astrocytic activation in response to amyloid-beta(1-42) (A beta(1-42)). The results demonstrate that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of A beta(1-42) deposits, suggesting a potential contribution of PD-linked LRRK2 to AD-related neuroinflammation and pathogenesis.
Article
Immunology
Kelly Ceyzeriat, Thomas Zilli, Philippe Millet, Nikolaos Koutsouvelis, Giovanna Dipasquale, Christine Fossey, Thomas Cailly, Frederic Fabis, Giovanni B. B. Frisoni, Valentina Garibotto, Benjamin B. B. Tournier
Summary: Low-dose brain radiation therapy has been shown to reduce neuroinflammation, lower amyloid levels, and improve cognitive performances in animal models of Alzheimer's disease.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Immunology
Deepali Singh
Summary: Neuroinflammation is caused by the misfiring of immune cells in the central nervous system and can have both positive and negative effects on neurodevelopment and post-injury tissue. Chronic or uncontrolled inflammatory responses may lead to neurodegenerative diseases, while abnormal activation of glial cells can mediate neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Chemistry, Physical
Mokshada Varma, Bhupendra Shravage, Sakharam Tayade, Avinash Kumbhar, Ray Butcher, Vinod Jani, Uddhavesh Sonavane, Rajendra Joshi, Prasad P. Kulkarni
Summary: Alzheimer's disease is a complex brain disorder involving multiple pathophysiological events, and targeting multiple mechanisms is necessary for its treatment. A novel methyl-substituted 3-acetylcoumarin thiosemicarbazone derivative shows potential in protecting against acetylcholinesterase activity, inflammation, and autophagy induction, as demonstrated in various cellular and animal models. The compound's molecular structure allows for better inhibition of AChE activity and peptide aggregation, suggesting promising therapeutic effects for AD.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Giulia Di Benedetto, Chiara Burgaletto, Maria Francesca Serapide, Rosario Caltabiano, Antonio Munafo, Carlo Maria Bellanca, Rosaria Di Mauro, Renato Bernardini, Giuseppina Cantarella
Summary: This study demonstrates the significant role of TRAIL-R2 in Aβ-related neurodegeneration and provides further evidence that the TRAIL system is a potential target for innovative AD therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shin-Meng Deng, Chia-Jung Chen, Hung-Lung Lin, Irene H. Cheng
Summary: Alzheimer's disease is a neurodegenerative disease with no effective prevention or treatment, but dietary modulation of the gut-brain axis can potentially delay the progression of AD by reducing neuroinflammation and alleviating cognitive deficits.
Review
Immunology
Cuicui Wang, Shuai Zong, Xiaolin Cui, Xueying Wang, Shuang Wu, Le Wang, Yingchao Liu, Zhiming Lu
Summary: Alzheimer's disease (AD) is a severe chronic degenerative neurological disease. The main pathogenic mechanism of AD is the pathological accumulation of beta-amyloid (A beta) peptides outside the cell. However, growing evidence suggests that this hypothesis cannot fully explain the pathogenesis of AD. Neuroinflammation plays a crucial role in AD development, as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes related to innate immune function.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Neurosciences
Guimei Zhang, Zicheng Wang, Huiling Hu, Meng Zhao, Li Sun
Summary: Alzheimer's disease is a common type of age-related dementia, where dysregulated microglia activity can lead to chronic neuroinflammation, promote pathological protein accumulation, and impair mitophagy. Targeting microglia may offer new therapeutic interventions for the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Hongtao Du, Jinzhi Song, Fang Ma, Hongxin Gao, Xinyan Zhao, Renjun Mao, Xiaolong He, Yan Yan
Summary: This study synthesised and characterised a series of novel harmine derivatives as potential ligands for AD treatment. Compounds 13 and 17d showed exceptional neuroprotective effects and potent inhibition against AChE and A beta aggregation. Kinetic studies and molecular modelling confirmed the interaction of compound 13 with both CAS and PAS of AChE.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marwa El-Hussieny, Mansoura A. Abd-El-Maksoud, Fouad M. Soliman, Marwa A. Fouad, Mohamed K. El-Ashrey
Summary: Alzheimer's disease is a neurodegenerative disease with no prevention or complete cure. In this study, researchers synthesized new triphenylphosphoranylidene derivatives and tested their biological activity against AChE and beta-amyloid proteins. The derivative 8c showed promising results as an AChE inhibitor, but lacked selectivity and had potential for structural modification to improve selectivity. Compound 8c also exhibited low cytotoxicity and showed good penetration into the blood-brain barrier and binding affinity with AChE.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Amir Dudai, Nadav Yayon, Hermona Soreq, Michael London
Summary: The urgent task of neuroscience is to understand how neuronal circuits operate, what causes them to fail, and how they can be repaired. This review focuses on a specific type of cortical neurons marked by the expression of VIP and ChAT, which can release both GABA and ACh. Despite their sparse population, these neurons may have a significant impact on cortical circuit function.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Katarzyna Winek, Hermona Soreq, Andreas Meisel
Summary: Cholinergic signaling plays a crucial role in cognitive processes, with cholinesterase inhibitors currently being the main treatment option for Alzheimer's disease and acute brain damage. The expression of cholinergic receptors in both neurons and glial cells suggests a connection to anti-inflammatory responses. Small noncoding RNA regulators, like microRNAs and transfer RNA fragments, may serve as promising biomarkers for predicting disease course and assessing treatment responses in neurological disorders.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Peripheral Vascular Disease
Nina Eikelis, John B. Dixon, Elisabeth A. Lambert, Geula Hanin, Yonat Tzur, David S. Greenberg, Hermona Soreq, Francine Z. Marques, Michael T. Fahey, Geoffrey A. Head, Markus P. Schlaich, Gavin W. Lambert
Summary: The study revealed an association between miR-132 and markers of cardiovascular and metabolic disease, suggesting that reduction of miR-132 may be a target for regulating liver lipid homeostasis and controlling obesity-related blood pressure.
JOURNAL OF HUMAN HYPERTENSION
(2022)
Editorial Material
Biochemistry & Molecular Biology
Lili Anglister, Israel Silman, Hermona Soreq
Summary: This special issue covers a wide range of topics and disciplines presented at the XVIth International Symposium on Cholinergic Mechanisms. The authors discuss recent developments in the field, including the association of cholinergic transmission with important neurological and neuromuscular diseases in the central and peripheral nervous systems.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Cell Biology
Christoph Erbacher, Shani Vaknine, Gilli Moshitzky, Sebastian Lobentanzer, Lina Eisenberg, Dimitar Evdokimov, Claudia Sommer, David S. Greenberg, Hermona Soreq, Nurcan Ueceyler
Summary: Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by musculoskeletal pain, fatigue, and a depressed mood. This study identified a specific microRNA signature (CholinomiRs) in FMS patients, which regulate immune-related gene expression.
Article
Clinical Neurology
Rachel E. Lackie, Aline S. de Miranda, Mei Peng Lim, Vladislav Novikov, Nimrod Madrer, Nadun C. Karunatilleke, Benjamin S. Rutledge, Stephanie Tullo, Anne Brickenden, Matthew E. R. Maitland, David Greenberg, Daniel Gallino, Wen Luo, Anoosha Attaran, Irina Shlaifer, Esther Del Cid Pellitero, Caroline Schild-Poulter, Thomas M. Durcan, Edward A. Fon, Martin Duennwald, Flavio H. Beraldo, M. Mallar Chakravarty, Timothy J. Bussey, Lisa M. Saksida, Hermona Soreq, Wing-Yiu Choy, Vania F. Prado, Marco A. M. Prado
Summary: The co-chaperone STI1 interacts with alpha-synuclein and plays a role in its misfolding and aggregation. Decreased STI1 function can reduce protein inclusion formation and improve motor and cognitive deficits caused by alpha-synuclein overexpression.
ACTA NEUROPATHOLOGICA
(2022)
Article
Neurosciences
Muslum Gok, Nimrod Madrer, Tamara Zorbaz, Estelle R. Bennett, David Greenberg, David A. Bennett, Hermona Soreq
Summary: Acetylcholinesterase and butyrylcholinesterase play important roles in Alzheimer's and Parkinson's diseases. The frequency of the functionally impaired BCHE-K variant is higher in AD and PD patients compared to controls. Changes in AChE and BChE levels are associated with the loss of cholinergic neurons in the brain of AD and PD patients.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Nadav Yayon, Oren Amsalem, Tamara Zorbaz, Or Yakov, Serafima Dubnov, Katarzyna Winek, Amir Dudai, Gil Adam, Anna K. Schmidtner, Marc Tessier-Lavigne, Nicolas Renier, Naomi Habib, Idan Segev, Michael London, Hermona Soreq
Summary: This study investigated the morphology and transcriptional diversity of cortical cholinergic VIP/ChAT interneurons (VChIs) and identified two distinct morphological types. After whisker deprivation, changes in dendritic arborization, cortical depth, and distribution patterns were observed in the barrel fields. The researchers also discovered key regulatory factors involved in morphological changes using a method for isolating nuclei from fixed tissues.
Article
Biochemistry & Molecular Biology
Iddo Paldor, Nimrod Madrer, Shani Vaknine Treidel, Dana Shulman, David S. Greenberg, Hermona Soreq
Summary: In this study, the expression levels of tRFs in cerebrospinal fluid (CSF) and blood were found to be distinct, with CSF showing higher levels of long tRFs. The CSF tRF profiles were also found to be significantly influenced by age, sex, and Parkinson's disease (PD), suggesting their potential as biomarkers for cerebral differences and neurological disorders. Furthermore, specific sets of tRFs in CSF and blood could differentiate PD patients from healthy controls. These findings highlight the importance of incorporating tRFs into future studies of CNS-related diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Patrick N. Pallier, Maria Ferrara, Francesca Romagnolo, Maria Teresa Ferretti, Hermona Soreq, Andrea Cerase
Summary: Research has shown that neurological and neuropsychiatric disorders affect men and women differently, but female participation in clinical trials and basic research is often overlooked, resulting in a poor understanding of the biological reasons behind these gender differences in disease development.
PROGRESS IN NEUROBIOLOGY
(2022)
Editorial Material
Neurosciences
Tobias Engel, Gary P. Brennan, Hermona Soreq
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Dana Shulman, Serafima Dubnov, Tamara Zorbaz, Nimrod Madrer, Iddo Paldor, David A. Bennett, Sudha Seshadri, Elliott J. Mufson, David S. Greenberg, Yonatan Loewenstein, Hermona Soreq
Summary: Females with Alzheimer's disease (AD) experience accelerated dementia and loss of cholinergic neurons compared to males, and the underlying mechanisms may involve changes in transfer RNA fragments (tRFs) targeting cholinergic transcripts (CholinotRFs). The study found that NAc CholinotRFs of mitochondrial genome origin had reduced levels, which correlated with elevations in their predicted cholinergic-associated mRNA targets. Single-cell RNA sequencing in AD temporal cortices also indicated altered sex-specific levels of cholinergic transcripts in diverse cell types and sex-specific CholinotRF elevations in neuroblastoma cells under cholinergic differentiation. These findings suggest the involvement of CholinotRFs in cholinergic regulation and their potential role in AD sex-specific cholinergic loss and dementia.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Hila Yehuda, Nimrod Madrer, Doron Goldberg, Hermona Soreq, Ari Meerson
Summary: An investigation using zebrafish larvae and adult zebrafish revealed differentially expressed RNA transcripts in anxiety and obesity models, with an inverse regulation of transcripts. These transcripts included long noncoding RNAs and transfer RNA fragments, and were associated with immune system and inflammation pathways. Interestingly, obesity in larvae did not exhibit anxiety-like behavior. These findings suggest an antagonistic pleiotropic phenomenon involving a re-adjusted modulation of the anxiety-metabolic links.
