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
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.
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
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
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
Pharmacology & Pharmacy
Isabel Garcia-Dorival, Miguel Angel Cuesta-Geijo, Lucia Barrado-Gil, Inmaculada Galindo, Urtzi Garaigorta, Jesus Urquiza, Ana del Puerto, Nuria E. Campillo, Ana Martinez, Pablo Gastaminza, Carmen Gil, Covadonga Alonso
Summary: The study found a novel interaction between the SARSCoV-2 nucleoprotein (N) and the cholesterol transporter NPC1, and identified compounds that can reduce viral infection, highlighting the importance of NPC1 for SARS-CoV-2 infection and suggesting a potential new therapeutic target against COVID-19.
ANTIVIRAL RESEARCH
(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
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
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
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
Neurosciences
Shiqian Han, Meng Ren, Tianyin Kuang, Mao Pang, Dongwei Guan, Yesong Liu, Yong Wang, Wengeng Zhang, Zhijia Ye
Summary: This study revealed dysregulated lncRNA expression patterns in NP-C disease, potentially playing a crucial role in its pathogenesis. RNA-seq analysis showed that mRNAs coexpressed with lncRNAs are mainly associated with immune system-related processes and neuroinflammation. Knockdown of specific lncRNAs could improve intracellular ROS levels and cell viability, as well as suppress inflammatory responses in vitro.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Martijn J. C. van der Lienden, Jan Aten, Andre R. A. Marques, Ingeborg S. E. Waas, Per W. B. Larsen, Nike Claessen, Nicole N. van der Wel, Roelof Ottenhoff, Marco van Eijk, Johannes M. F. G. Aerts
Summary: Niemann-Pick type C (NPC) disease is caused by impaired cholesterol efflux from lysosomes, and deficiency in lysosomal proteins like NPC1 may lead to abnormal levels of GCase and GBA2, as well as markers of lipid-stressed macrophages in the liver. The overexpression of LIMP2 in hepatocytes of NPC1(-/-) liver suggests a potential role in cholesterol export and protection of hepatocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Laura L. Baxter, Dawn E. Watkins-Chow, Nicholas L. Johnson, Nicole Y. Farhat, Frances M. Platt, Ryan K. Dale, Forbes D. Porter, William J. Pavan, Jorge L. Rodriguez-Gil
Summary: This study validates the use of LysoTracker as a predictor for age of onset and disease severity in NPC1 patients, using primary fibroblasts from a large cohort. The study also identifies a set of genes significantly associated with lysosomal defects or age of onset, particularly neurological symptom onset, and shows distinct expression patterns of these genes among patient subgroups.
SCIENTIFIC REPORTS
(2022)
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
Endocrinology & Metabolism
Jenny Serra-Vinardell, Neus Roca-Ayats, Laura De-Ugarte, Lluisa Vilageliu, Susanna Balcells, Daniel Grinberg
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Niamh X. Cawley, Anna T. Lyons, Daniel Abebe, Christopher A. Wassif, Forbes D. Porter
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell & Tissue Engineering
Jenny Serra-Vinardell, Maxwell B. Sandler, Evgenia Pak, Wei Zheng, Amalia Dutra, Wendy Introne, William A. Gahl, May Christine Malicdan
STEM CELL RESEARCH
(2020)
Article
Endocrinology & Metabolism
Antony Cougnoux, Julia C. Yerger, Mason Fellmeth, Jenny Serra-Vinardell, Christopher A. Wassif, Niamh X. Cawley, Forbes D. Porter
MOLECULAR GENETICS AND METABOLISM
(2020)
Article
Genetics & Heredity
Evangelia Dimitriou, Marina Moraitou, Monica Cozar, Jenny Serra-Vinardell, Lluisa Vilageliu, Daniel Grinberg, Irene Mavridou, Helen Michelakakis
MOLECULAR GENETICS AND METABOLISM REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Niamh X. Cawley, Anna T. Lyons, Daniel Abebe, Rachel Luke, Julia Yerger, Rebecca Telese, Christopher A. Wassif, Joan E. Bailey-Wilson, Forbes D. Porter
Summary: Complex asparagine-linked glycosylation plays a critical role in cellular functions. The deficiency of MGAT5, a key enzyme involved in this process, leads to increased severity of NPC1 disease in mice. The reduction in asparagine-linked glycosylation is associated with the progression of NPC1 disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Julia Yerger, Antony C. Cougnoux, Craig B. Abbott, Rachel Luke, Tannia S. Clark, Niamh X. Cawley, Forbes D. Porter, Cristin D. Davidson
Summary: Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. Clinical manifestations in patients and mammalian models offer translational value. Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. A comprehensive, easy-to-follow phenotypic assessment based on a composite scoring system has been developed and verified using murine models of NPC disease. This scoring system can be applied to other neurodegenerative disease models exhibiting motor incoordination, increasing its utility in translational studies.
Article
Biochemistry & Molecular Biology
Jenny Serra-Vinardell, Maxwell B. Sandler, Raffaella De Pace, Javier Manzella-Lapeira, Antony Cougnoux, Keyvan Keyvanfar, Wendy J. Introne, Joseph A. Brzostowski, Michael E. Ward, William A. Gahl, Prashant Sharma, May Christine C. Malicdan
Summary: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the LYST gene. This study shows that LYST-deficient human neuronal models exhibit lysosome depletion and hyperelongated tubules protruding from autolysosomes, which is also observed in neurons derived from CHS patients' induced pluripotent stem cells (iPSCs). The results suggest that LYST plays a crucial role in autophagic lysosome reformation (ALR) by ensuring the correct fission of autolysosome tubules and being recruited to the lysosome membrane.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Correction
Biochemistry & Molecular Biology
Jenny Serra-Vinardell, Maxwell B. Sandler, Raffaella De Pace, Javier Manzella-Lapeira, Antony Cougnoux, Keyvan Keyvanfar, Wendy J. Introne, Joseph A. Brzostowski, Michael E. Ward, William A. Gahl, Prashant Sharma, May Christine V. Malicdan
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)