Article
Medicine, Research & Experimental
Anna Scotto Rosato, Einar K. Krogsaeter, Dawid Jaslan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Boeck, Amanda Wyatt, Daniela Wuenkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber-Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl-Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L. Medina, Dominik Paquet, Christian Grimm
Summary: This study found that TPC2 activation can improve cellular phenotypes associated with LSDs, including cholesterol or lipofuscin accumulation and abnormal vacuole formation. Validation in patient cells and mouse models suggests that TPC2 is a promising target for the treatment of different types of LSDs.
EMBO MOLECULAR MEDICINE
(2022)
Review
Chemistry, Medicinal
Marcos Morales-Tenorio, Tiziana Ginex, Miguel Angel Cuesta-Geijo, Nuria E. Campillo, Cesar Munoz-Fontela, Covadonga Alonso, Rafael Delgado, Carmen Gil
Summary: The Niemann-Pick C1 (NPC1) receptor plays a crucial role in regulating intracellular cholesterol trafficking and facilitating the entry of Ebola virus into host cells. Disruption of the NPC1/EBOV-GP interaction could be a promising strategy for developing drugs to inhibit viral entry and infection, although further research is needed to understand the molecular and structural details of this interaction.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Jiang Du, Xinlei Liu, Yan Zhang, Xiaojing Han, Chunya Ma, Yanli Liu, Lihong Guan, Liang Qiao, Juntang Lin
Summary: This study found that combination treatment with HP beta CD and metformin did not prolong survival time or increase body weight in Npc1(-/-) mice, but it reduced inflammatory response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Shiqian Han, Qijun Wang, Yongfeng Song, Mao Pang, Chunguang Ren, Jing Wang, Dongwei Guan, Wei Xu, Fangyong Li, Fengchao Wang, Xinyuan Zhou, Carlos Fernandez-Hernando, Huiwen Zhang, Dianqing Wu, Zhijia Ye
Summary: Niemann-Pick disease type C (NP-C) is a genetic lysosomal disorder with limited therapeutic options. This study demonstrates that lithium treatment improves phenotypes and extends survival in NP-C mouse models by suppressing STING activation, SREBP2 processing, and target gene expression. Lithium impedes STING/SREBP2 transport, providing a mechanistic explanation for its effects. This reveals a potential therapeutic option for NP-C patients and a strategy to reduce active STING/SREBP2 pathway.
Article
Multidisciplinary Sciences
Ting-Ting Chu, Xintao Tu, Kun Yang, Jianjun Wu, Joyce J. Repa, Nan Yan
Summary: This study identifies a cGAS- and cGAMP-independent mode of STING activation that affects neuropathology and provides a therapeutic target for the treatment of Niemann-Pick disease type C.
Article
Biochemical Research Methods
Wenping Li, Melissa R. R. Pergande, Christopher A. A. Crutchfield, Brian C. C. Searle, Peter S. S. Backlund, Jaqueline A. A. Picache, Kathryn Burkert, Nicole M. M. Yanjanin-Farhat, Paul S. S. Blank, Cynthia L. L. Toth, Christopher A. A. Wassif, Forbes D. D. Porter, Stephanie M. M. Cologna
Summary: Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease characterized by endo/lysosomal accumulation of unesterified cholesterol and sphingolipids. In this study, CSF samples from NPC1 individuals and controls were used to identify protein biomarkers. Pro-neuropeptide Y (NPY) was found to be significantly increased in NPC1 individuals, but levels were comparable to controls in individuals treated with miglustat. NPY could be a potential therapeutic target for NPC1 due to its roles in attenuating neuroinflammation and reducing excitotoxicity.
Article
Medicine, Research & Experimental
Denzil Furtado, Christina Cortez-Jugo, Ya Hui Hung, Ashley I. Bush, Frank Caruso
Summary: Researchers successfully used NPC1-encoded mRNA to combat protein insufficiency and pathogenic phenotype caused by biallelic NPC1 mutations, achieving treatment for the rare disease NP-C1. The gene engineering strategies greatly improved the expression efficiency of the mRNA.
MOLECULAR PHARMACEUTICS
(2022)
Article
Genetics & Heredity
Jorge L. Rodriguez-Gil, Simona E. Bianconi, Nicole Farhat, David E. Kleiner, Marie Nelson, Forbes D. Porter
Summary: Niemann-Pick disease type C (NPC) is a rare and fatal disorder characterized by neurodegeneration and hepatic involvement. Patients with NPC have an increased risk of hepatocellular carcinoma, suggesting the need for screening in this population.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Biology
Cristin D. Davidson, Alana L. Gibson, Tansy Gu, Laura L. Baxter, Benjamin E. Deverman, Keith Beadle, Arturo A. Incao, Jorge L. Rodriguez-Gil, Hideji Fujiwara, Xuntian Jiang, Randy J. Chandler, Daniel S. Ory, Viviana Gradinaru, Charles P. Venditti, William J. Pavan
Summary: Niemann-Pick C1 disease (NPC1) is a rare, fatal neurodegenerative disease caused by mutations in NPC1 gene, resulting in cholesterol accumulation in lysosomes and leading to neurological complications. AAV-PHP.B vector shows greater efficiency in transducing the central nervous system of Npc1 mutant mice compared to AAV9, indicating potential for improved gene therapy in NPC1.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Pilar Guatibonza Moreno, Luba M. M. Pardo, Catarina Pereira, Sabine Schroeder, Deepthi Vagiri, Ligia S. S. Almeida, Carlos Juaristi, Heba Hosny, Clarice C. Y. Loh, Anika Leubauer, Galina Torres Morales, Sebastian Oppermann, Marius-Ionut Iurascu, Steffen Fischer, Tara-Marisa Steinicke, Nikenza Viceconte, Claudia Cozma, Krishna Kumar Kandaswamy, Jorge Pinto Basto, Tobias Boettcher, Peter Bauer, Aida Bertoli-Avella
Summary: Niemann-Pick type C1 disease is a rare and severe autosomal recessive disorder characterized by neurovisceral clinical manifestations. This study analyzed the clinical, genetic, and biomarker data of 602 patients diagnosed with NPC1, finding that biomarkers may indicate disease severity and progression.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Priyanka Kannan, Madhana Priya Nanda Kumar, Nithya Rathinam, D. Thirumal Kumar, Magesh Ramasamy
Summary: This study analyzes the mutational effect in NPC protein of Niemann-Pick disease type C using computational tools, and performs molecular docking and molecular dynamics simulation to understand the effectiveness and stability of the drug.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Shiqian Han, Huiwen Zhang, Mengni Yi, Xiaoqing Liu, Gustavo H. B. Maegawa, Yunding Zou, Qijun Wang, Dianqing Wu, Zhijia Ye
Summary: This study evaluated the safety and feasibility of lithium carbonate in NP-C1 patients and found that lithium treatment significantly reduced plasma 7-ketocholesterol concentrations, improved NPC Neurological Severity Scores, and enhanced swallowing capacity. Patients tolerated lithium well with no serious adverse events recorded.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Anika Prabhu, Insung Kang, Raffaella De Pace, Christopher A. Wassif, Hideji Fujiwara, Pamela Kell, Xuntian Jiang, Daniel S. Ory, Juan S. Bonifacino, Michael E. Ward, Forbes D. Porter
Summary: Niemann-Pick disease type C is a childhood-onset neurodegenerative disorder caused by mutations in NPC1 or NPC2 genes. A novel human iPSC-derived neuronal model of NPC1 has been developed, recapitulating key pathological features and showing potential for high-throughput drug screening.
Review
Cell Biology
Irfan Ahmad, Seyede Narges Fatemi, Mohammad Ghaheri, Ali Rezvani, Dorsa Azizi Khezri, Mohammad Natami, Saman Yasamineh, Omid Gholizadeh, Zahra Bahmanyar
Summary: Viruses communicate with their hosts through interactions with proteins, lipids, and carbohydrates on the plasma membrane. The large endo/lysosomal membrane protein Niemann-Pick C1 (NPC1) is an essential intracellular receptor for viral infection and a potential therapeutic target for treating viral illnesses. NPC1 plays a crucial role in viral entry, replication, and infection by controlling cholesterol levels.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Carsten Holzmann, Martin Witt, Arndt Rolfs, Veronica Antipova, Andreas Wree
Summary: In a mouse model of Niemann-Pick disease type C1 (NPC1), combination treatment (COMBI) and individual treatments with MIGLU or HPssCD were beneficial in terms of body and brain weight, with differences observed based on gender. While all treatments had some beneficial effects on evaluated parameters, locomotor activity reduction was not significantly improved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Carsten Holzmann, Martin Witt, Arndt Rolfs, Veronica Antipova, Andreas Wree
Summary: In a mouse model of Niemann-Pick disease type C1 (NPC1), combination treatment (COMBI) and individual treatments with MIGLU or HPssCD were beneficial in terms of body and brain weight, with differences observed based on gender. While all treatments had some beneficial effects on evaluated parameters, locomotor activity reduction was not significantly improved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Nicole Power Guerra, Alisha Parveen, Daniel Buehler, David Leon Brauer, Luisa Mueller, Kristin Pilz, Martin Witt, Aenne Glass, Rika Bajorat, Deborah Janowitz, Olaf Wolkenhauer, Brigitte Vollmar, Angela Kuhla
Summary: Exercise, dietary adjustments, and time-restricted feeding are the only successful long-term treatments for obesity. The combination of dietary change and treadmill exercise effectively reduces weight, fat, and FGF21 levels in obese mice, while also decreasing anxious behavior, increasing overall activity, and improving olfactory detection abilities. Feature selection algorithms identified FGF21 and body weight as highly weighted features related to improved behavior in obese mice after weight reduction.
Article
Food Science & Technology
Veronica Antipova, Carsten Holzmann, Alexander Hawlitschka, Martin Witt, Andreas Wree
Summary: The study found that intrastriatal injection of Botulinum neurotoxin-A (BoNT-A) can reduce depression-like behavior in hemi-Parkinsonian rats, but did not have a significant effect on anxiety-like behavior.
Article
Anatomy & Morphology
Isabel Gross, Tabea Tschigor, Angelina L. Salman, Fan Yang, Jiankai Luo, Danara Vonk, Mark S. Hipp, John Neidhardt, Anja U. Braeuer
Summary: The study investigated the mRNA expression levels of Prgs during mouse brain development and found different spatio-temporal expression patterns. The uncharacterized Prg4 was highly expressed throughout brain development, but unlike its close family members, it does not seem to affect cell morphology.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Food Science & Technology
Teresa Alberts, Veronica Antipova, Carsten Holzmann, Alexander Hawlitschka, Oliver Schmitt, Jens Kurth, Jan Stenzel, Tobias Lindner, Bernd J. Krause, Andreas Wree, Martin Witt
Summary: Olfactory deficits observed in Parkinson's disease cannot be completely explained by the 6-OHDA hemi-PD rat model, but injection of BoNT-A can improve olfactory performance by increasing the availability of D-2/D3R in the olfactory bulb.
Article
Pediatrics
Katarzyna Mackowiak-Lewandowicz, Danuta Ostalska-Nowicka, Katarzyna Zaorska, Elzbieta Kaczmarek, Jacek Zachwieja, Martin Witt, Michal Nowicki
Summary: By studying the expression pattern of lipid metabolism and kidney damage markers in obese adolescents, it is possible to predict the risk of developing CKD. Increased serum concentrations of cholesterol, triglycerides, and urine concentration of neutrophil gelatinase-associated lipocalin may serve as potential predictors for CKD development in obese adolescents.
PEDIATRIC NEPHROLOGY
(2022)
Article
Neurosciences
Isabel Gross, Nicola Brandt, Danara Vonk, Franziska Koeper, Lars Woehlbrand, Ralf Rabus, Martin Witt, Axel Heep, Torsten Ploesch, Mark S. Hipp, Anja U. Braeuer
Summary: This study analyzes the expression and localization of PRG5 in the mouse brain, and finds its association with dendritic spine formation and stabilization. PRG5 is highly expressed in areas with regenerative capacity and specifically expressed in the late phase of adult neurogenesis.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Lina-Marielle Krysewski, Nicole Power Guerra, Annika Glatzel, Carsten Holzmann, Veronica Antipova, Oliver Schmitt, Libo Yu-Taeger, Huu Phuc Nguyen, Andreas Wree, Martin Witt
Summary: This study investigated olfactory deficits in a transgenic rat model of Huntington's disease (HD). The results suggest that the main olfactory epithelium (MOE) is temporarily affected in HD, while the vomeronasal (VNE) remains relatively stable.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nicola Brandt, Jan Philipp Willmer, Maurilyn S. Ayon-Olivas, Veronika Banicka, Martin Witt, Andreas Wree, Isabel Gross, Anne Glaeser, Jens Hausmann, Anja U. Braeuer
Summary: The C-termini of PRG3 and PRG5 play a critical role in shaping early neuronal morphology, but the results suggest that the C-terminus alone might not be sufficient for promoting the morphological effects induced by PRG3 and PRG5.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Veronica Antipova, Lisa-Marie Steinhoff, Carsten Holzmann, Arndt Rolfs, Carlos Junior Hempel, Martin Witt, Andreas Wree
Summary: This study analyzed the alterations of organ weights in Npc1 mice under different treatment strategies. The results showed that Npc1(-/-) mice had smaller weights in the heart, liver, kidneys, testes, and glands, while female Npc1(-/-) mice had significantly smaller ovaries and uteri.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Anatomy & Morphology
A. U. Braeuer, J. Sevecke-Rave, A. Glaeser, P. Nahrath, T. Hummel, M. Witt
Summary: This study provides an optimized protocol for extracting large amounts of RNA from human nasal mucosal biopsies. The protocol improves the yield and quality of RNA, allowing for the analysis of multiple genes in qRT-PCR experiments.
Article
Health Care Sciences & Services
Alhassan Ali Ahmed, Agnieszka Brychcy, Mohamed Abouzid, Martin Witt, Elzbieta Kaczmarek
Summary: Our study aims to investigate the knowledge of using AI and ML methods in the clinical field in pathologists in Poland. Most pathologists in this study did not use AI or ML models, highlighting the importance of increasing awareness and educational programs regarding applying AI and ML in medical diagnosis.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Anatomy & Morphology
Julia Koenig, Anja Rahn, Jana Schaetzel, Marcus Frank, Thomas Stahnke, Martin Witt, Angrit Stachs, Oliver Stachs, Inga Langner, Tobias Lindner, Ebba Beller, Dagmar-C. Fischer, Felix Streckenbach
Summary: This study investigated the effects of prenatal ultrasound on fetal development using a chicken embryo model. It was found that pulsed-wave Doppler ultrasound (PWD) had an inhibitory effect on cell proliferation in the developing chicken retina. These findings highlight the need for further research on the impact of ultrasound on fetal development.
ANATOMIA HISTOLOGIA EMBRYOLOGIA
(2023)
Meeting Abstract
Behavioral Sciences
Sema Kaya, Carsten Holzmann, Markus Kipp, Martin Witt
Meeting Abstract
Behavioral Sciences
Nicole Power Guerra, Alisha Parveen, Daniel Buhler, David Leon Brauer, Luisa Muller, Kristin Pilz, Martin Witt, Anne Glass, Rika Bajorat, Deborah Jannowitz, Olaf Wolkenhauer, Brigitte Vollmar, Angela Kuhla