Review
Cell Biology
Fayaz Ahmad Mir, Ayeman Amanullah, Buddhi Prakash Jain, Zeeshan Hyderi, Akash Gautam
Summary: Gene expression in the brain undergoes significant changes during memory acquisition, recall, and forgetfulness. Non-genetic factors such as environmental elements, epigenetic changes, and lifestyle have gained attention in understanding the causes of neurodegenerative diseases and age-related dementia. Epigenetic modifications play a crucial role in regulating gene expression in all living organisms. Genes associated with aging and memory disorders related to neurodegeneration are regulated by epigenetic processes including DNA methylation, histone acetylation, and mRNA editing. Understanding the mechanisms behind these epigenetic changes could lead to effective treatments for neurodegeneration and age-induced dementia.
AGEING RESEARCH REVIEWS
(2023)
Article
Biology
Alicia Tapias, David Lazaro, Bo-Kun Yin, Seyed Mohammad Mahdi Rasa, Anna Krepelova, Erika Kelmer Sacramento, Paulius Grigaravicius, Philipp Koch, Joanna Kirkpatrick, Alessandro Ori, Francesco Neri, Zhao-Qi Wang
Summary: The study reveals the importance of TRRAP for neuroprotection and the network connecting TRRAP, HAT, and SP1 in regulating microtubule dynamics.
Article
Biology
Stefan A. Zukin, Matthew R. Marunde, Irina K. Popova, Katarzyna M. Soczek, Eva Nogales, Avinash B. Patel
Summary: The structure of the central hub of the NuA4 protein complex, which connects the histone acetyltransferase (HAT) and Trimer Independent of NuA4 involved in Transcription Interactions with Nucleosomes (TINTIN) modules, has been determined. The HAT module recognizes nucleosomes with hyperacetylated H3 tails, while the TINTIN module recognizes nucleosomes with hyperacetylated H2A and H4 tails. This study provides insights into how NuA4 is recruited to specific genomic sites.
Article
Plant Sciences
Shuangshuang Yang, Lei Fan, Rui Zhang, Chenghuan Song, Jiyun Shi, Jing Wang, Pingao Zhang, Hao Wang, Yongfang Zhang
Summary: This study demonstrates that SMI extracted from Asparagus cochinchinensis (Lour.) Merr. can provide neuroprotective effects by increasing the expression of P300 protein, thereby upregulating histone acetylation levels in the promoter region of BDNF, which provides an important theoretical basis for the treatment of Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Disha Agarwal, Ruchika Kumari, Ashal Ilyas, Shweta Tyagi, Rajnish Kumar, Nitesh Kumar Poddar
Summary: Epigenetics has opened a new dimension in exploring unanswered questions in genetics, particularly in neurodegenerative diseases like Alzheimer's and cancers. The alterations in DNA methylation levels, histone acetylation, and methylation play a significant role in conditions such as Alzheimer's disease. Studying the interplay between the mTOR regulatory pathway and epigenetic machinery may lead to early diagnosis and novel therapeutic strategies for Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Daniel Schator, Sonia Mondino, Jeremy Berthelet, Cristina Di Silvestre, Mathilde Ben Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser, Monica Rolando
Summary: Legionella pneumophilia secretes more than 300 effectors, including RomA and LphD, via a type IV secretion system. RomA methylates histone H3 at K14 to counteract host immune responses, while LphD deacetylates H3K14 to work synergistically with RomA. The two effectors target host chromatin and bind the HBO1 histone acetyltransferase complex to regulate histone modifications.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Svenja Koenig, Nadine Schmidt, Karin Bechberger, Sarah Morris, Mercedes Priego, Hannah Zaky, Yuyu Song, Jan Pielage, Silke Brunholz, Scott T. Brady, Stefan Kins, Gerardo Morfini
Summary: This study evaluated the intracellular effects of the amyloid precursor protein (APP) intracellular domain (AICD) on axonal transport. The results showed that AICD inhibits fast axonal transport (FAT), which is a deficit observed in neurons affected by Alzheimer's disease (AD). Further experiments revealed that this inhibitory effect is related to aberrant activation of axonal kinases and phosphorylation of the anterograde motor protein conventional kinesin. Pharmacological inhibitors of these kinases alleviated the inhibitory effect of AICD on FAT. Deletion experiments indicated that this effect requires a sequence encompassing the NPTY motif in AICD and interacting axonal proteins containing a phosphotyrosine-binding domain. These findings provide evidence for axon-specific effects of AICD and suggest a potential mechanistic framework linking alterations in APP processing, FAT deficits, and axonal pathology in AD.
Article
Multidisciplinary Sciences
Pan Jia, Xiang Li, Xuelei Wang, Liangjiao Yao, Yingying Xu, Yu Hu, Wenwen Xu, Zhe He, Qifan Zhao, Yicong Deng, Yi Zang, Meiyu Zhang, Yan Zhang, Jun Qin, Wei Lu
Summary: ZMYND8 forms liquid compartments with NF-kappa B/p65 to silence latent SEs and restrict macrophage-mediated inflammation, providing a potential mechanism to fine-tune latent SEs in a spatiotemporal manner.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Quanshu Wu, Qiuyue Huang, Huilin Guan, Xiaoni Zhang, Manzhu Bao, Mohammed Bendahmane, Xiaopeng Fu
Summary: The exposure of rose plants to high temperature affects their growth and development. Research shows that histone acetylation, a dynamic and reversible process mediated by histone deacetylases (HDAC) and histone acetyltransferases (HAT), plays an important role in plant development and response to stress. In this study, the identification and analysis of HDAC and HAT genes in the Rosa chinensis 'Old Blush' genome provided insights into the potential molecular mechanisms underlying rose plants' response to high-temperature conditions.
Article
Neurosciences
Prachetas J. Patel, Yong Ren, Zhen Yan
Summary: Epigenetic aberrations, especially the altered DNA binding of CTCF, are associated with transcriptional alterations in AD. Reduced CTCF binding is observed on genes related to synaptic organization, cell adhesion, and actin cytoskeleton, leading to decreased mRNA expression. The disrupted 3D chromatin organization controlled by CTCF may contribute to the pathogenesis of AD.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Lee-Ann Niekerk, Mogamat Fahiem Carelse, Olalekan Olanrewaju Bakare, Vuyo Mavumengwana, Marshall Keyster, Arun Gokul
Summary: The review discusses the negative impact of heavy metals such as cadmium on staple crop production and the role of epigenetic mechanisms in enhancing cadmium tolerance. Understanding and utilizing these genetic mechanisms can provide a crucial framework for improving plant cadmium tolerance in future studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Yingbin Lin, Anlan Lin, Lili Cai, Weibin Huang, Shanzhi Yan, Yuanxiang Wei, Xinglin Ruan, Wenting Fang, Xiaoman Dai, Jinbo Cheng, Jie Zhang, Wanjin Chen, Qinyong Ye, Xiaochun Chen, Jing Zhang
Summary: Nuclear acetyl-CoA pools, regulated by ACSS2, play a role in histone acetylation and cognitive function in AD patients. Reduced ACSS2 expression and histone acetylation levels were observed in AD patients and 5 x FAD mice. Upregulation of ACSS2 or acetate administration restored synaptic plasticity and cognitive function in AD mice.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Mariah Beaver, Bhanu Chandra Karisetty, Haolin Zhang, Akanksha Bhatnagar, Ellen Armour, Visha Parmar, Reshma Brown, Merry Xiang, Felice Elefant
Summary: The study in Drosophila brains revealed that disruptions in gene control in Alzheimer's Disease are predominantly seen in neuronal genes, with Tip60 HAT and HDAC2 playing a key role in this process. Additionally, transcription factor binding sites near Tip60/HDAC2 co-peaks in neuronal genes may be involved in coenzyme recruitment.
Article
Cell Biology
Yimei Cai, Tao Cui, Pengqi Yin, Paxton Paganelli, Stefano Vicini, Tingting Wang
Summary: Synaptic homeostatic plasticity is essential for maintaining the stability of synaptic and neural functions in the nervous system. Impairment of this regulation has been linked to synaptic destabilization in Alzheimer's disease (AD). Through integrative computational and genetic studies in Drosophila, the researchers identified specific glial genes that are dysregulated in AD and are crucial for regulating synaptic homeostatic plasticity. Their findings provide evidence connecting abnormal glial transcriptomic changes in AD with the impairment of homeostatic plasticity.
Article
Plant Sciences
Na Song, Jingchen Lin, Xingbei Liu, Zehui Liu, Debiao Liu, Wei Chu, Jinpeng Li, Yongming Chen, Shumin Chang, Qun Yang, Xiaoyu Liu, Weilong Guo, Mingming Xin, Yingyin Yao, Huiru Peng, Zhongfu Ni, Chaojie Xie, Qixin Sun, Zhaorong Hu
Summary: In this study, a histone acetyltransferase (TaHAG1) was identified as a positive regulator of powdery mildew resistance in wheat. TaHAG1 regulates expression of the key transducer gene TaPAD4 and promotes the accumulation of SA and reactive oxygen species to enhance resistance to powdery mildew. Furthermore, TaHAG1 interacts with TaPLATZ5 and together they potentiate the expression of TaPAD4 by increasing the levels of H3 acetylation. This discovery provides valuable insights into improving disease resistance in wheat and other crops.
Article
Transplantation
Sergio C. Lopez-Garcia, Mallory L. Downie, Ji Soo Kim, Olivia Boyer, Stephen B. Walsh, Tom Nijenhuis, Svetlana Papizh, Pallavi Yadav, Ben C. Reynolds, Stephane Decramer, Martine Besouw, Manel Perello Carrascosa, Claudio La Scola, Francesco Trepiccione, Gema Ariceta, Aurelie Hummel, Claire Dossier, John A. Sayer, Martin Konrad, Mandy G. Keijzer-Veen, Atif Awan, Biswanath Basu, Dominique Chauveau, Leire Madariaga, Linda Koster-Kamphuis, Monica Furlano, Miriam Zacchia, Pierluigi Marzuillo, Yincent Tse, Ismail Dursun, Ayse Seda Pinarbasi, Despoina Tramma, Ewout J. Hoorn, Ibrahim Gokce, Kathleen Nicholls, Loai A. Eid, Lisa Sartz, Michael Riordan, Nakysa Hooman, Nikoleta Printza, Olivier Bonny, Pedro Arango Sancho, Raphael Schild, Rajiv Sinha, Stefano Guarino, Victo Martinez Jimenez, Lidia Rodriguez Pena, Hendrica Belge, Olivier Devuyst, Tanja Wlodkowski, Francesco Emma, Elena Levtchenko, Nine V. A. M. Knoers, Daniel G. Bichet, Franz Schaefer, Robert Kleta, European NDI Consortium, Detlef Bockenhauer
Summary: The study of a large NDI cohort showed overall favorable outcomes with normal adult height and mild to moderate chronic kidney disease. However, lower educational achievement and the presence of urological and mental health problems in over half of the patients were noted.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Clinical Neurology
Joshua Stevenson-Hoare, Amanda Heslegrave, Ganna Leonenko, Dina Fathalla, Eftychia Bellou, Lauren Luckcuck, Rachel Marshall, Rebecca Sims, Bryan Paul Morgan, John Hardy, Bart de Strooper, Julie Williams, Henrik Zetterberg, Valentina Escott-Price
Summary: Plasma biomarkers for Alzheimer's disease-related pathologies have made significant progress in recent years, with well-validated blood tests available for the detection of amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. This study demonstrates that a combination of five plasma biomarkers, along with genetic variants associated with these biomarkers, can be used to accurately diagnose and predict the onset of Alzheimer's disease.
Editorial Material
Urology & Nephrology
P. Toby Coates, Germaine Wong, Brad H. Rovin, Pierre Ronco
KIDNEY INTERNATIONAL
(2022)
Article
Transplantation
Helena Baechle, Peggy Sekula, Pascal Schlosser, Inga Steinbrenner, Yurong Cheng, Fruzsina Kotsis, Heike Meiselbach, Helena Stockmann, Sebastian Schoenherr, Kai-Uwe Eckardt, Olivier Devuyst, Juergen Scherberich, Anna Koettgen, Ulla T. Schultheiss
Summary: This study aimed to explore metabolites associated with uromodulin concentrations and evaluate their association with the progression of chronic kidney disease (CKD) and adverse kidney events. The study found that higher levels of urinary and serum uromodulin were associated with a lower risk of adverse kidney events, suggesting a potential protective role of functional nephrons in CKD outcomes.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
Yong Li, Yurong Cheng, Francesco Consolato, Guglielmo Schiano, Michael R. Chong, Maik Pietzner, Ngoc Quynh H. Nguyen, Nora Scherer, Mary L. Biggs, Marcus E. Kleber, Stefan Haug, Burulca Goecmen, Marie Pigeyre, Peggy Sekula, Inga Steinbrenner, Pascal Schlosser, Christina B. Joseph, Jennifer A. Brody, Morgan E. Grams, Caroline Hayward, Ulla T. Schultheiss, Bernhard K. Kraemer, Florian Kronenberg, Annette Peters, Jochen Seissler, Dominik Steubl, Cornelia Then, Matthias Wuttke, Winfried Maerz, Kai-Uwe Eckardt, Christian Gieger, Eric Boerwinkle, Bruce M. Psaty, Josef Coresh, Peter J. Oefner, Guillaume Pare, Claudia Langenberg, Jurgen E. Scherberich, Bing Yu, Shreeram Akilesh, Olivier Devuyst, Luca Rampoldi, Anna Koettgen
Summary: Uromodulin (UMOD) is a major risk gene for kidney disease and is highly abundant in urine. This study identified genetic variants associated with circulating uromodulin and found an upstream variant in the UMOD locus that affects its synthesis in kidney cells. The study also found shared association patterns between UMOD and complex traits like chronic kidney disease. Furthermore, the study revealed the role of glycan marks and their enzymes and receptors in uromodulin glycosylation.
Review
Physiology
Olivier Devuyst, Murielle Bochud, Eric Olinger
Summary: The identification of genetic factors associated with kidney disease can provide insights into its mechanisms and potential therapies. Technological advances in the last two decades have greatly advanced our understanding of the genetic architecture of chronic kidney disease. This review focuses on the UMOD gene, which codes for a kidney-specific protein, to demonstrate how genetic variation can contribute to a spectrum of kidney disorders. The study of genetic factors in disease pathogenesis and prognosis has significant therapeutic implications.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Ophthalmology
Adele Ehongo, Noelie Bacq, Nacima Kisma, Artemise Dugauquier, Yassir Alaoui Mhammedi, Kevin Coppens, Francoise Bremer, Karelle Leroy
Summary: This study compares the peripapillary polar characteristics in eyes with peripapillary staphyloma and gamma peripapillary atrophy, and examines the presence of peripapillary intrachoroidal cavitation (PICC). The study finds that the wedge-shaped deformity and suprachoroidal detachment are more frequent in eyes with PICC, and they are aligned with the subarachnoid space.
CLINICAL OPHTHALMOLOGY
(2022)
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Article
Urology & Nephrology
Olivier Devuyst, Krzysztof Kiryluk
KIDNEY INTERNATIONAL
(2023)
Article
Clinical Neurology
Sebastiaan Moonen, Marta J. Koper, Evelien Van Schoor, Jolien M. Schaeverbeke, Rik Vandenberghe, Christine A. F. von Arnim, Thomas Tousseyn, Bart De Strooper, Dietmar Rudolf Thal
Summary: The study investigated the contribution of pyroptosis, a pro-inflammatory mechanism of cell death downstream of the inflammasome, to neurodegeneration in Alzheimer's disease (AD). The findings suggest the activation of pyroptosis in specific cell types and its potential link to neuron death in AD.
ACTA NEUROPATHOLOGICA
(2023)
Article
Transplantation
Ines P. D. Costa, Nicolas Hautem, Gugliemo Schiano, Shinichi Uchida, Tomoya Nishino, Olivier Devuyst
Summary: The study reveals that AQP1 and AQP7 are abundantly expressed in the peritoneal membrane. While AQP1 facilitates water transport during peritoneal dialysis, the role of AQP7 in glycerol transport during fasting is unknown. The findings show that fasting increases the expression of AQP1 and AQP7 in the peritoneum, leading to structural and functional changes that improve fluid removal.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Cell Biology
Kunie Ando, Siranjeevi Nagaraj, Fahri Kucukali, Marie-Ange De Fisenne, Andreea-Claudia Kosa, Emilie Doeraene, Lidia Lopez Gutierrez, Jean-Pierre Brion, Karelle Leroy
Summary: This article provides an overview of the current knowledge about the PICALM gene, including its physiological functions, genetic variants, post-translational modifications, and relevance to Alzheimer's disease pathogenesis.
Article
Multidisciplinary Sciences
Nathalie Kyalu Ngoie Zola, Clemence Balty, Sebastien Pyr dit Ruys, Axelle A. T. Vanparys, Nicolas D. G. Huyghe, Gaetan Herinckx, Manuel Johanns, Emilien Boyer, Pascal Kienlen-Campard, Mark H. Rider, Didier Vertommen, Bernard J. Hanseeuw
Summary: Tau isoforms in insoluble aggregates differ between tauopathies, but not in soluble brain extracts. This study characterizes the post-translational modifications of aggregated and soluble tau protein in various tauopathies, revealing specific soluble signatures for each tauopathy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Rajeshwar Narlawar, Lutgarde Serneels, Celia Gaffric, Harrie J. M. Gijsen, Bart De Strooper, Francois Bischoff
Summary: This paper describes the rational design, synthesis, structure-activity relationship (SAR), and biological profile of selective gamma-secretase inhibitors for presenilin-1 (PSEN-1) complex. The study analyzes known inhibitors to understand the characteristics required for selective inhibition, and uses this knowledge to design and synthesize a new class of brain-penetrant inhibitors. The compound (+)-13b shows high potency and selectivity towards PSEN1-APH1B complex, making it a promising candidate for further lead optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Sriram Balusu, Katrien Horre, Nicola Thrupp, Katleen Craessaerts, An Snellinx, Lutgarde Serneels, Dries T'Syen, Iordana Chrysidou, Amaia M. Arranz, Annerieke Sierksma, Joel Simren, Thomas K. Karikari, Henrik Zetterberg, Wei-Ting Chen, Dietmar Rudolf Thal, Evgenia Salta, Mark Fiers, Bart De Strooper
Summary: Neuronal cell loss is a defining feature of Alzheimer's disease (AD), and this study reveals that the up-regulation of long noncoding RNA MEG3 is strongly associated with AD. The overexpression of MEG3 induces necroptosis in human neurons, leading to significant neuronal cell loss. However, down-regulating MEG3 or inhibiting necroptosis could rescue neuronal cell loss in a mouse model of AD, suggesting potential therapeutic approaches for AD.