Article
Biochemistry & Molecular Biology
Danuta Drozdowska, Dawid Maliszewski, Agnieszka Wrobel, Artur Ratkiewicz, Michal Sienkiewicz
Summary: Eleven new benzamides were synthesized and one derivative showed the strongest inhibitory activity against acetylcholinesterase and beta-secretase. Molecular modeling revealed that the compound increased the enzyme's stiffness and reduced its flexibility to inhibit the enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Katrin Pratsch, Chie Unemura, Mana Ito, Stefan F. Lichtenthaler, Naotaka Horiguchi, Jochen Herms
Summary: This study investigated the effect of highly selective BACE1 inhibitors on dendritic spine dynamics in the somatosensory cortex of mice. The results showed that if soluble Sez6 (sSez6) levels drop too much, highly selective BACE1 inhibitors can alter dendritic spine density similar to non-selective inhibitors. Therefore, carefully adjusting the dosing to achieve an appropriate amount of Sez6 cleavage may be reasonable.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Smith Patel, Ankush Vardhaman Bansoad, Rakesh Singh, Gopal L. Khatik
Summary: This article discusses the importance of BACE1 in regulating the progression of Alzheimer's disease (AD) and the development of BACE1 inhibitors. Despite the challenges involved in developing BACE1 inhibitors, some inhibitors have reached advanced stages of clinical trials. BACE1 inhibitors have the potential to be the most effective therapeutic approach in delaying or preventing AD progression.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sara Badesso, Paz Cartas-Cejudo, Maria Espelosin, Enrique Santamaria, Mar Cuadrado-Tejedor, Ana Garcia-Osta
Summary: DHA, as the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging and may lower the risk for developing Alzheimer's disease. DHA enhances memory function through promoting synapse formation and has potential for dietary supplement for AD dementia prevention.
Article
Biochemistry & Molecular Biology
Nikita Zernov, Alexander V. Veselovsky, Vladimir V. Poroikov, Daria Melentieva, Anastasia Bolshakova, Elena Popugaeva
Summary: A new selective TRPC6 agonist, C20, has been identified, which can recover cognitive deficits caused by synaptic loss in the brains of Alzheimer's disease patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Agriculture, Multidisciplinary
Jian Bao, Zheng Liang, Xiaokang Gong, Yanna Zhao, Mengjuan Wu, Wei Liu, Chenyu Tu, Xiaochuan Wang, Xiji Shu
Summary: This study found that Tangeretin (TAN) exhibits antidementia activity in APPswe/PSEN1dE9 transgenic mice, reducing cognitive impairment, synaptic impairments, and beta-amyloid accumulations. TAN also showed powerful inhibitory activity against beta-secretase, suggesting it as a potential drug for preventing Alzheimer's disease pathology.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Inge Tomic, Laura Schwindt, Dominic Helm, Mandy Rettel, Walter Schulz-Schaeffer, Elmar Krause, Jens Rettig, Klaus Fassbender, Yang Liu
Summary: Deficiency of p38 alpha-MAPK in neurons leads to increased retrograde transportation of BACE1 in axons, shifting it from axonal terminals to lysosomes in the cell body, which exacerbates amyloid deposition in the brain of Alzheimer's disease.
Article
Medicine, Research & Experimental
Marika Marino, Lujia Zhou, Melvin Y. Rincon, Zsuzsanna Callaerts-Vegh, Jens Verhaert, Jerome Wahis, Eline Creemers, Lidia Yshii, Keimpe Wierda, Takashi Saito, Catherine Marneffe, Iryna Voytyuk, Yessica Wouters, Maarten Dewilde, Sandra Duque, Cecile Vincke, Yona Levites, Todd E. Golde, Takaomi C. Saido, Serge Muyldermans, Adrian Liston, Bart De Strooper, Matthew G. Holt
Summary: Single domain antibodies (VHHs) have potential therapeutic value for neurological disorders, but their use in the central nervous system is limited by the blood-brain barrier. This study proposes a gene transfer strategy using BBB-crossing AAV-based vectors to deliver VHH directly into the CNS. The results show that AAV-delivered VHH can effectively inhibit BACE1 and improve cognitive performance in an Alzheimer's disease mouse model, providing a novel therapeutic approach for neurodegenerative diseases.
EMBO MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Marie Tautou, Sabiha Eddarkaoui, Florian Descamps, Paul-Emmanuel Larchanche, Jamal El Bakali, Liesel Mary Goveas, Melanie Dumoulin, Chloe Lamarre, David Blum, Luc Buee, Patricia Melnyk, Nicolas Sergeant
Summary: The study identified two molecules, MAGS02-14 and PEL24-199, with ss-secretase modulatory effects in cellulo. PEL24-199 was shown to restore short-term memory and reduce neurofibrillary degeneration, suggesting that lysosomotropic activity may not be essential for the effect on tau pathology.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Elizabeth B. Wright, Erik G. Larsen, Cecilia M. Coloma-Roessle, Hannah R. Hart, Martha R. C. Bhattacharya
Summary: Loss of TMEM184B affects synaptic gene expression and anxiety-related behaviors, suggesting a potential link to neurodevelopmental disorders.
Article
Chemistry, Medicinal
Lailiang Qu, Limei Ji, Cheng Wang, Heng Luo, Shang Li, Wan Peng, Fucheng Yin, Dehua Lu, Xingchen Liu, Lingyi Kong, Xiaobing Wang
Summary: The selenium-containing compound 13f, based on ebselen and verubecestat, showed potential anti-Alzheimer's disease and antioxidant stress effects by reducing beta-amyloid production and alleviating oxidative stress. Furthermore, 13f also demonstrated anti-inflammatory and cytoprotective effects, making it a promising candidate for AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Danish Iqbal, Md Tabish Rehman, Mohamed F. Alajmi, Mohammed Alsaweed, Qazi Mohammad Sajid Jamal, Sharifa M. Alasiry, Awatif B. Albaker, Munerah Hamed, Mehnaz Kamal, Hind Muteb Albadrani
Summary: In search of a new natural cure for Alzheimer's disease (AD), researchers targeted multiple key regulatory proteins and conducted virtual screening and molecular dynamics simulation (MDS) to identify a promising compound. F1094-0201 emerged as a potent multitarget inhibitor, exhibiting strong binding interactions with GSK3 beta, NMDA receptor, and BACE-1. Analysis indicated its suitability for CNS drug-likeness and stable association with the target proteins. The compound's free energies supported its potential as a therapeutic option for managing AD-related pathways.
Review
Pharmacology & Pharmacy
Bruno P. Imbimbo, Stefania Ippati, Mark Watling, Camillo Imbimbo
Summary: According to the beta-amyloid (A beta) hypothesis, brain A beta accumulation is the primary cause of cognitive deficit and dementia in Alzheimer's disease (AD). While many anti-A beta drugs have failed in clinical trials, recent studies have shown encouraging results for antibodies that clear amyloid plaques. These findings suggest that decreased levels of soluble monomeric A beta may be the main driver of AD, rather than the aggregated forms.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Geriatrics & Gerontology
Arezou Sayad, Sajad Najafi, Bashdar Mahmud Hussen, Sara Tharwat Abdullah, Ahmad Movahedpour, Mohammad Taheri, Mohammadreza Hajiesmaeili
Summary: BACE1 and BACE1-AS play important roles in regulating amyloid deposition and neurodegenerative diseases, and their dysregulation is associated with the development of various human diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Mater H. Mahnashi, Muhammad Ayaz, Mehreen Ghufran, Ibrahim Abdullah Almazni, Omaish Alqahtani, Bandar A. Alyami, Yahya S. Alqahtani, Haider Ali Khan, Abdul Sadiq, Muhammad Waqas
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral abnormalities. Current drugs for AD have limited efficacy, so there is a need for new compounds. This study investigated the inhibitory potential of natural bioactive compounds against key enzymes involved in AD and found that epigallocatechin-3-gallate may be a candidate for AD treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Neurosciences
Kaichuan Zhu, Xianyuan Xiang, Severin Filser, Petar Marinkovic, Mario M. Dorostkar, Sophie Crux, Ulf Neumann, Derya R. Shimshek, Gerhard Rammes, Christian Haass, Stefan F. Lichtenthaler, Jenny M. Gunnersen, Jochen Herms
BIOLOGICAL PSYCHIATRY
(2018)
Article
Biochemistry & Molecular Biology
Tobias Brummer, Martina Pigoni, Armando Rossello, Huanhuan Wang, Peter J. Noy, Michael G. Tomlinson, Carl P. Blobel, Stefan F. Lichtenthaler
Article
Multidisciplinary Sciences
Mirsada Causevic, Kristina Dominko, Martina Malnar, Lea Vidatic, Stjepko Cermak, Martina Pigoni, Peer-Hendrik Kuhn, Alessio Colombo, Daniel Havas, Stefanie Flunkert, Jessica McDonald, Jenny M. Gunnersen, Birgit Hutter-Paier, Sabina Tahirovic, Manfred Windisch, Dimitri Krainc, Stefan F. Lichtenthaler, Silva Hecimovic
Article
Multidisciplinary Sciences
Huimeng Wang, Criselle D'Souza, Xin Yi Lim, Lyudmila Kostenko, Troi J. Pediongco, Sidonia B. G. Eckle, Bronwyn S. Meehan, Mai Shi, Nancy Wang, Shihan Li, Ligong Liu, Jeffrey Y. W. Mak, David P. Fairlie, Yoichiro Iwakura, Jennifer M. Gunnersen, Andrew W. Stent, Dale I. Godfrey, Jamie Rossjohn, Glen P. Westall, Lars Kjer-Nielsen, Richard A. Strugnell, James McCluskey, Alexandra J. Corbett, Timothy S. C. Hinks, Zhenjun Chen
NATURE COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
Simone D. Scilabra, Martina Pigoni, Veronica Pravata, Tobias Schaetzl, Stephan A. Mueller, Linda Troeberg, Stefan F. Lichtenthaler
SCIENTIFIC REPORTS
(2018)
Article
Neurosciences
Amelia Nash, Timothy D. Aumann, Martina Pigoni, Stefan F. Lichtenthaler, Hiroshi Takeshima, Kathryn M. Munro, Jenny M. Gunnersen
Article
Biochemistry & Molecular Biology
Finn Peters, Hazal Salihoglu, Katrin Pratsch, Etienne Herzog, Martina Pigoni, Carmelo Sgobio, Stefan F. Lichtenthaler, Ulf Neumann, Jochen Herms
Article
Behavioral Sciences
Christopher W. Butler, Yvette M. Wilson, Samuel A. Mills, Jenny M. Gunnersen, Mark Murphy
NEUROBIOLOGY OF LEARNING AND MEMORY
(2020)
Article
Biochemistry & Molecular Biology
Martina Pigoni, Hung-En Hsia, Jana Hartmann, Jasenka Rudan Njavro, Merav D. Shmueli, Stephan A. Mueller, Goekhan Guener, Johanna Tueshaus, Peer-Hendrik Kuhn, Rohit Kumar, Pan Gao, Mai Ly Tran, Bulat Ramazanov, Birgit Blank, Agnes L. Hipgrave Ederveen, Julia Von Blume, Christophe Mulle, Jenny M. Gunnersen, Manfred Wuhrer, Gerhard Rammes, Marc Aurel Busche, Thomas Koeglsperger, Stefan F. Lichtenthaler
Article
Multidisciplinary Sciences
Bruna Paulsen, Silvia Velasco, Amanda J. Kedaigle, Martina Pigoni, Giorgia Quadrato, Anthony J. Deo, Xian Adiconis, Ana Uzquiano, Rafaela Sartore, Sung Min Yang, Sean K. Simmons, Panagiotis Symvoulidis, Kwanho Kim, Kalliopi Tsafou, Archana Podury, Catherine Abbate, Ashley Tucewicz, Samantha N. Smith, Alexandre Albanese, Lindy Barrett, Neville E. Sanjana, Xi Shi, Kwanghun Chung, Kasper Lage, Edward S. Boyden, Aviv Regev, Joshua Z. Levin, Paola Arlotta
Summary: This study utilized organoid models of the human cerebral cortex to identify cell-type-specific developmental abnormalities resulting from haploinsufficiency in ASD risk genes SUV420H1, ARID1B, and CHD8. The research found asynchronous development of cortical neuronal lineages and distinct molecular pathways associated with these mutations. The study revealed shared cell-type-specific neurodevelopmental abnormalities across ASD risk genes in a manner influenced by individual genomic context.
Article
Neurosciences
Maria Roitman, Laura E. Edgington-Mitchell, Jon Mangum, James Ziogas, Alexios A. Adamides, Paul Myles, Hearan Choo-Bunnett, Nigel W. Bunnett, Jenny M. Gunnersen
Article
Neurosciences
C. W. Butler, Y. M. Wilson, J. Oyrer, T. J. Karle, S. Petrou, J. M. Gunnersen, M. Murphy, C. A. Reid