Article
Biochemistry & Molecular Biology
Francois Ancien, Fabrizio Pucci, Marianne Rooman
Summary: SMPD1 plays a crucial role in sphingolipid metabolism, and genetic variants are linked to disorders like Niemann-Pick disease. The SMPD1-ZooM algorithm accurately predicts disease-causing variants, highlighting the importance of aromatic interactions for SMPD1 function and stability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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
Medicine, General & Internal
Moein Mobini, Shabnam Radbakhsh, Francyne Kubaski, Peyman Eshraghi, Saba Vakili, Rahim Vakili, Manijeh Khalili, Majid Varesvazirian, Tannaz Jamialahmadi, Seyed Ali Alamdaran, Seyed Javad Sayedi, Omid Rajabi, Seyed Ahmad Emami, Zeljko Reiner, Amirhossein Sebkar
Summary: This pilot study assessed the potential efficacy of trehalose treatment in patients with Niemann-Pick disease types A and B. The results showed improvement in health-related quality of life, serum biomarkers, and organomegaly after 3 months of treatment. Although not statistically significant, these findings are encouraging and should be further explored.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Chemistry, Applied
Diego Navarro-Barreda, Begona Bedrina, Cesar A. A. Angulo-Pachon, Juan F. F. Miravet, Dolores Perez-Sala, Francisco Galindo
Summary: Four new BODIPY derivatives were synthesized and characterized, with a focus on their effects on cellular uptake, intracellular location, and fluorescence imaging abilities. The results showed that one of the new molecules displayed superior lysosomal location compared to the others.
Article
Biochemistry & Molecular Biology
Nina H. Pipalia, Syed Z. Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S. J. Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S. Ory, Frederick R. Maxfield
Summary: Inhibition of HSP90 clears cholesterol from LE/Ly in NPC1(I1061T) fibroblasts and enhances delivery of mutant NPC1(I1061T) protein. Additionally, HSP90 inhibition increases HSP70 expression, and overexpression of HSP70 reduces cholesterol storage in NPC1(I1061T) fibroblasts. This suggests that HSP90 inhibitors may improve NPC1 protein folding and relieve cholesterol accumulation in NPC1 mutant fibroblasts by increasing other chaperones.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Chemistry, Medicinal
Renshuai Zhang, Wenjing Liu, Jun Zeng, Jingsen Meng, Hongfei Jiang, Jie Wang, Dongming Xing
Summary: Cholesterol is a critical component of cell membranes, but elevated serum cholesterol levels are a major risk factor for heart disease. Understanding and developing NPC1L1 inhibitors, which can decrease cholesterol absorption, is an important research direction that presents both challenges and exciting therapeutic opportunities.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, General & Internal
Erdos Melinda
Summary: Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by enzyme deficiency or protein deficiency, leading to the accumulation of sphingomyelin and cholesterol in cells. Early genetic testing is crucial for diagnosis and treatment, with substrate reduction and enzyme replacement therapies showing promise in alleviating symptoms and slowing disease progression.
Article
Biophysics
Emilio J. Gonzalez-Ramirez, Asier Etxaniz, Alicia Alonso, Felix M. Goni
Summary: Lipidomic analysis revealed differences in the N-acyl components of sphingolipids between brain tissue and other mammalian tissues. The high levels of C18:0 and C16:0 in brain and non-brain sphingomyelin (SM) were important due to the abundance of SM in the plasma membrane. This study investigated the properties of C16:0 and C18:0 sphingolipids and their impact on membrane rigidity using various experimental techniques.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Graciela Arguello, Elisa Balboa, Pablo J. Tapia, Juan Castro, Maria Jose Yanez, Pamela Mattar, Rodrigo Pulgar, Silvana Zanlungo
Summary: Niemann-Pick type C disease (NPCD) is a lysosomal storage disease characterized by abnormal cholesterol accumulation in lysosomes. Activation of transcription factor EB (TFEB) by genistein can correct pathological phenotypes in NPC models by improving lysosomal function and autophagic flux. These results suggest that genistein-mediated TFEB activation could be a potential therapeutic agent for treating NPCD and other LSDs with neurological compromise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgu, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, Edward Schuchman
Summary: Background Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. In this study, clinical guidelines for the diagnosis and management of ASMD patients were developed through literature review and expert experiences. The guidelines provide conclusive statements and score them based on evidence, recommendations, and expert opinions. The guidelines aim to improve the quality of care for ASMD patients, with or without enzyme replacement therapy (ERT).
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Anouk G. Groenen, Anouk M. La Rose, Mengying Li, Venetia Bazioti, Arthur F. Svendsen, Niels J. Kloosterhuis, Albertina Ausema, Alle Pranger, M. Rebecca Heiner-Fokkema, Klary E. Niezen-Koning, Tom Houben, Ronit Shiri-Sverdlov, Marit Westerterp
Summary: This study found that elevated G-CSF levels and HSC mobilization may contribute to splenomegaly in patients with NPC1 disease.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Developmental Biology
Wei-Chia Tseng, Ana J. Johnson Escauriza, Chon-Hwa Tsai-Morris, Benjamin Feldman, Ryan K. Dale, Christopher A. Wassif, Forbes D. Porter
Summary: NPC is a rare, fatal neurodegenerative lysosomal disease caused by mutations in NPC1 or NPC2, resulting in the accumulation of cholesterol and other lipids in the lysosome and reduction in cellular cholesterol bioavailability.
Article
Cell Biology
Joseph C. Roney, Sunan Li, Tamar Farfel-Becker, Ning Huang, Tao Sun, Yuxiang Xie, Xiu-Tang Cheng, Mei-Yao Lin, Frances M. Platt, Zu-Hang Sheng
Summary: NPC is a neurodegenerative disorder characterized by lipid accumulation, and the impaired lysosome delivery into axons due to elevated cholesterol on lysosome membranes may contribute to axonal autophagosome accumulation and neuron death. Pharmacologic reduction of lysosomal membrane cholesterol can rescue lysosome transport and reduce axonal autophagic stress.
DEVELOPMENTAL CELL
(2021)
Article
Genetics & Heredity
Jiayue Hu, Gustavo H. B. Maegawa, Xia Zhan, Xiaolan Gao, Yu Wang, Feng Xu, Wenjuan Qiu, Lianshu Han, Xuefan Gu, Huiwen Zhang
Summary: Niemann-Pick disease Types A and B are caused by variants in the SMPD1 gene, with significant correlations between laboratory findings and clinical presentations. Various SMPD1 variants were associated with different clinical forms of NPA/B. This study contributes to understanding the natural history of the disease and developing effective treatments.