Article
Plant Sciences
Min-Ji Jung, Namkwon Kim, Seung Ho Jeon, Min Sung Gee, Ji-Woon Kim, Jong Kil Lee
Summary: The study investigated the effects of eugenol on Alzheimer's disease (AD) and found that eugenol effectively improved cognitive function and reduced pathological changes in 5xFAD mice. The underlying mechanisms may involve inhibiting neuronal cell death and promoting beta-amyloid clearance.
Review
Immunology
Lauren H. Fairley, Jia Hui Wong, Anna M. Barron
Summary: Alzheimer's disease is a terminal neurodegenerative disease with innate immune dysfunction playing a significant role in its pathogenesis. Microglia, the effector cells of innate immunity in the brain, have important immune functions that are energetically demanding and regulated by mitochondria. Genetic risk factors and pathology associated with AD can impair microglial metabolic programming, leading to immune dysfunction. Targeting microglial metabolism may offer a therapeutic window for treating Alzheimer's disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Yun Li, Xiaohuan Xia, Yi Wang, Jialin C. Zheng
Summary: This review summarizes the latest progress on the relationship between mitochondrial dysfunction and microglial activation in AD, highlighting the importance of studying this relationship and potential therapeutic strategies.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Biochemistry & Molecular Biology
Jasvinder Singh Bhatti, Satinder Kaur, Jayapriya Mishra, Harikrishnareddy Dibbanti, Arti Singh, Arubala P. Reddy, Gurjit Kaur Bhatti, P. Hemachandra Reddy
Summary: Alzheimer's disease (AD) is a neurodegenerative disease that involves synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, and accumulation of amyloid & beta; and phosphorylated Tau. Targeting mitochondrial proteins, including dynamin-related protein 1 (Drp1), may be a potential therapeutic approach for preventing AD pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Pharmacology & Pharmacy
Zhiwei Xue, Lei Ye, Jianwei Ge, Zhen Lan, Xinxin Zou, Chenglu Mao, Xinyu Bao, Linjie Yu, Yun Xu, Xiaolei Zhu
Summary: In this study, the researchers found that the inhibition of ABHD6 could improve synaptic function and memory impairment in APP/PS1 mice with Alzheimer's disease, without affecting the levels of amyloid-beta and neuroinflammation in the brain. Injection of the ABHD6-specific inhibitor wwl70 enhanced synaptic plasticity and memory function, lowered amyloid-beta levels and neuroinflammation, and promoted the phagocytosis of amyloid-beta by microglia.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hannah Ennerfelt, Coco Holliday, Daniel A. Shapiro, Kristine E. Zengeler, Ashley C. Bolte, Tyler K. Ulland, John R. Lukens
Summary: Recent advances have shown the importance of microglia-expressed innate immune receptors in Alzheimer's disease (AD), specifically TREM2, CD33, and CD22. However, the downstream signaling molecules used by these receptors in AD are still not well understood. This study demonstrates that CARD9, an intracellular adaptor molecule, plays a crucial role in A(3-mediated disease and microglial responses in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Clinical Neurology
Rebecca L. Winfree, Mabel Seto, Logan Dumitrescu, Vilas Menon, Philip De Jager, Yanling Wang, Julie Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman
Summary: This study investigated the correlation between region-specific TREM2 mRNA expression and neuropathology measures in a large sample size. The results showed that TREM2 expression was related to Alzheimer's disease pathology, cerebrovascular pathology, microglial activation, and cognitive decline, but the associations varied across different brain regions. These findings suggest that TREM2's pathological associations are dependent on the brain region.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Tatsuhiro Ayabe, Chika Takahashi, Rena Ohya, Yasuhisa Ano
Summary: Beta-lactolin improves mitochondrial functions and prevents neuronal cell death in Alzheimer's disease-related neuronal cell models, demonstrating its advantage in maintaining neuronal health.
Review
Biochemistry & Molecular Biology
Zdenek Fisar
Summary: Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with A beta neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of A beta oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly A beta oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.
Article
Multidisciplinary Sciences
Daniel C. Ellwanger, Shoutang Wang, Simone Brioschi, Zhifei Shao, Lydia Green, Ryan Case, Daniel Yoo, Dawn Weishuhn, Palaniswami Rathanaswami, Jodi Bradley, Sara Rao, Diana Cha, Peng Luan, Shilpa Sambashivan, Susan Gilfillan, Samuel A. Hasson, Ian N. Foltz, Menno van Lookeren Campagne, Marco Colonna
Summary: TREM2 plays a critical role in microglia activation trajectories, with ligand engagement being essential for certain activation pathways. Activation trajectories induced by stimuli are more prominent in female mice than male mice. Injection of hT2AB can replenish depleted microglial pools lacking certain activation trajectories.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Aiste Jekabsone, Silvija Jankeviciute, Katryna Pampuscenko, Vilmante Borutaite, Ramune Morkuniene
Summary: This study found that small oligomers of A beta(1-42) can produce neurotoxic effects through microglial NMDAR activation and changes in mitochondrial redox states, suggesting a promising strategy for AD therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Shuta Ozawa, Yukiko Hori, Yusuke Shimizu, Atsuhiko Taniguchi, Takanobu Suzuki, Wenbo Wang, Yung Wen Chiu, Reiko Koike, Satoshi Yokoshima, Tohru Fukuyama, Sho Takatori, Youhei Sohma, Motomu Kanai, Taisuke Tomita
Summary: The study demonstrated that photo-oxygenation facilitates the clearance of aggregated amyloid-beta from the brains of living Alzheimer's disease model mice, and enhances the microglial degradation of amyloid-beta peptide, suggesting a novel strategy for Alzheimer's disease treatment that may be compatible with immunotherapy.
Article
Biochemistry & Molecular Biology
Xuexia Li, Qingqing Shi, Hao Xu, Yufang Xiong, Chao Wang, Linfeng Le, Junliang Lian, Guoli Wu, Feiyuan Peng, Qiong Liu, Xiubo Du
Summary: This study found that Ebselen can improve cognitive abilities, restore synaptic damage, and repair damaged mitochondrial morphology and function in AD mice by protecting the mitochondria.
Article
Biochemistry & Molecular Biology
Xia Zhao, Jinfeng Sun, Li Xiong, Lingyu She, Liwei Li, Hao Tang, Yuqing Zeng, Fan Chen, Xue Han, Shiju Ye, Wei Wang, Xu Wang, Guang Liang
Summary: Dectin-1, a pattern recognition receptor, is involved in microglia-mediated neuroinflammation and the development of Alzheimer's disease (AD). It directly binds to beta-amyloid (Aβ), activating downstream signaling pathways and inducing the expression of inflammatory factors and AD pathology.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lee-Way Jin, Jacopo Di Lucente, Ulises Ruiz Mendiola, Nopparat Suthprasertporn, Alexey Tomilov, Gino Cortopassi, Kyoungmi Kim, Jon J. Ramsey, Izumi Maezawa
Summary: This study investigated the impact of BHB on AβO-stimulated hiMG and found that BHB can mitigate inflammation and mitochondrial damage caused by AβO, rectify MKP, and restore cellular function. The authors suggest that these effects of BHB may contribute to the therapeutic benefits of ketogenic diet intervention in aged mice and individuals with mild AD.
Article
Biochemical Research Methods
Vigneshwaran Namasivayam, Katja Stefan, Katja Silbermann, Jens Pahnke, Michael Wiese, Sven Marcel Stefan
Summary: This study successfully extracted molecular structural features of inhibitors of the model protein family of ATP-binding cassette (ABC) transporters using a feature-driven computer-aided pattern analysis (C@PA) method and expanded the known multitarget modulator landscape of pan-ABC transporter inhibitors.
Article
Dermatology
Antonia Reimer-Taschenbrecker, Axel Kuenstner, Misa Hirose, Stefanie Huebner, Stella Gewert, Saleh Ibrahim, Hauke Busch, Cristina Has
Summary: Children with recessive dystrophic epidermolysis bullosa experience early changes in their skin microbiome, with a predominance of Staphylococcus aureus in wounded and unwounded skin. Changes in oral mucosal and gut microbiome are less significant. The abundance of S. aureus is correlated with wound burden and disease activity.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biology
Viola von Bohlen Und Halbach, Simone Venz, Simon Nwakor, Christian Hentschker, Elke Hammer, Heike Junker, Andreas W. Kuss, Oliver von Bohlen Und Halbach, Lars R. Jensen
Summary: The study found that FTSJ1 deficiency in mice resulted in altered neuronal plasticity in the hippocampal area, both morphologically and physiologically. These changes may contribute to impaired learning and memory functions.
Article
Chemistry, Medicinal
Sachin Puri, Katja Stefan, Sharuk L. Khan, Jens Pahnke, Sven Marcel Stefan, Kapil Juvale
Summary: A new MCT1 modulator with potent inhibitory and anticancer activities, selective against MCT4, was discovered. The lead compound also showed significant inhibitory effects against ABCB1 and reversed multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Neurosciences
Oliver von Bohlen, Halbach
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Shiraz Dib, Rodrigo Azevedo Loiola, Emmanuel Sevin, Julien Saint-Pol, Fumitaka Shimizu, Takashi Kanda, Jens Pahnke, Fabien Gosselet
Summary: Neuroinflammation and brain lipid imbalances are observed in individuals with Alzheimer's disease. The tumor necrosis factor-a (TNFa) and liver X receptor (LXR) signaling pathways are involved in both processes, but their relationships in human brain pericytes (HBP) of the neurovascular unit are not well understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Sanjeev Gumber, Fawn Connor-Stroud, Dustin Howard, Xiaodong Zhang, Brenda J. Bradley, Chet C. Sherwood, Lary C. Walker
Summary: A 57-year-old female chimpanzee exhibited increasing lethargy and rapidly progressing lower-limb weakness, with postmortem examination revealing the presence of polyglucosan bodies (PGBs) in the spinal cord. These findings represent the first description of PGBs associated with neurological dysfunction in a chimpanzee, resembling adult PGB disease in humans.
Article
Multidisciplinary Sciences
Antoine Gagelin, Corentin Largeau, Sandrine Masscheleyn, Mathilde S. S. Piel, Daniel Calderon-Mora, Frederic Bouillaud, Jerome Henin, Bruno Miroux
Summary: By combining molecular dynamic simulations with in vivo functional assays, Gagelin et al. uncovered the molecular features of UCP1 that are essential for its inhibition by nucleotides. The study focused on understanding how purine nucleotides inhibit the respiration uncoupling activity of UCP1. Through simulations and assays, the authors identified specific residues and interactions that play a crucial role in the selective inhibition of UCP1 by purine nucleotides.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Pablo Bascunana, Mirjam Brackhan, Luisa Moehle, Jingyun Wu, Thomas Bruening, Ivan Eiriz, Baiba Jansone, Jens Pahnke
Summary: Alzheimer's disease is the most common cause of dementia, and the use of fingolimod as a treatment for Alzheimer's disease is controversial. The effectiveness of fingolimod treatment depends on the stage at which it is administered. In this study, treatment with fingolimod only reduced A beta load in male animals in the late treatment group, while no other treatment groups showed any differences compared to the control group.
Article
Biochemistry & Molecular Biology
Simone Venz, Viola von Bohlen Und Halbach, Christian Hentschker, Heike Junker, Andreas Walter Kuss, Thomas Sura, Elke Krueger, Uwe Voelker, Oliver von Bohlen Und Halbach, Lars Riff Jensen, Elke Hammer
Summary: A workflow for tandem mass spectrometry-based protein profiling of immunohistochemistry specimens was established and applied to tissue sections. The CA1 region of the hippocampus was investigated using protein extraction and digestion methods followed by mass spectrometry measurement and data analysis. Literature searches and Gene Ontology annotation verified the applicability of this method for global protein profiling using formalin-fixed and embedded material and previously used immunohistochemistry slides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Luisa Moehle, Katja Stefan, Pablo Bascunana, Mirjam Brackhan, Thomas Bruening, Ivan Eiriz, Ahmed El Menuawy, Sylvie van Genderen, Irene Santos-Garcia, Anna Maria Gorska, Maria Villa, Jingyun Wu, Sven Marcel Stefan, Jens Pahnke
Summary: Reusing drugs may accelerate the development of effective dementia treatment. However, the drug dimethyl fumarate was found to be inefficient in reducing Alzheimer's disease-related changes in the brain due to the involvement of an essential brain transporter.
Article
Anatomy & Morphology
Julia Sophie Ehlers, Katharina Bracke, Viola von Bohlen Und Halbach, Florian Siegerist, Nicole Endlich, Olivervon Bohlen Und Halbach
Summary: The SLC35F1 gene mutation in humans is associated with neurodevelopmental disorders. However, Slc35f1-deficient mice do not exhibit obvious deficits in learning and memory, and neuroanatomical parameters of neuronal plasticity are also unaffected. Therefore, they do not display a neurodevelopmental phenotype.
BRAIN STRUCTURE & FUNCTION
(2023)
Article
Chemistry, Medicinal
Sachin Puri, Katja Stefan, Sharuk L. Khan, Jens Pahnke, Sven Marcel Stefan, Kapil Juvale
Summary: Researchers synthesized a library of indole-based compounds and discovered that one of these compounds (compound 24) has potential for cancer treatment. This compound inhibits MCT1, prevents cancer cell proliferation, induces apoptosis, and has the ability to reverse multidrug resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Johanne U. Hermansen, Dorota M. Wojcik, Nina Robinson, Jens Pahnke, Hans Kristian Haugland, Ann Helen Jamtoy, Trond Flaegstad, Hanne Halvorsen, Bendik Lund, Lars O. Baumbusch, Monica C. Munthe-Kaas
Summary: This study aimed to establish a prospective and centralized biobank for infants, children, and adolescents diagnosed with cancer in Norway. With judicial and ethical approvals obtained through a consortium, steering committee, and advisory board, pipelines including SOPs for all aspects of the biobank process were developed. By January 1, 2021, approximately 12,000 samples from 510 patients had been included, with a 96% consent and participation rate among newly diagnosed patients.