Review
Biochemistry & Molecular Biology
I. Basak, H. E. Wicky, K. O. McDonald, J. B. Xu, J. E. Palmer, H. L. Best, S. Lefrancois, S. Y. Lee, L. Schoderboeck, S. M. Hughes
Summary: Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease caused by mutations in thirteen CLN genes. Mutations in the CLN5 gene lead to a form of variant late-infantile NCL, with widespread protein expression in various tissues. Research on CLN5 helps to understand lysosomal biology and develop efficient therapies for CLN5 Batten disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemical Research Methods
Andreas Tuermer, Simone Mausbach, Edgar Kaade, Markus Damme, Marc Sylvester, Volkmar Gieselmann, Melanie Thelen
Summary: Neuronal ceroid lipofuscinoses (NCLs) are the most prevalent inherited neurodegenerative diseases in childhood, characterized by autofluorescence storage material deposition in lysosomes, leading to symptoms like seizures, blindness, and premature mortality. Dysfunction of CLN6, a transmembrane protein in the endoplasmic reticulum, causes variant late infantile NCL (vLINCL) and affects lysosomal integrity. Study results showed that Cln6 dysfunction is directly linked to changes in the lysosomal compartment and other forms of NCL.
Article
Geriatrics & Gerontology
Qiang Huang, Yong-Fang Zhang, Lin-Jie Li, Eric B. Dammer, Yong-Bo Hu, Xin-Yi Xie, Ran Tang, Jian-Ping Li, Jin-Tao Wang, Xiang-Qian Che, Gang Wang, Ru-Jing Ren
Summary: Neuronal ceroid lipofuscinosis (NCL) is a group of inherited neurodegenerative diseases characterized by the presence of lipofuscin deposits in the lysosomal lumen. In this study, a novel C128Y mutation in the DNAJC5 gene was identified in a young Chinese female with adult-onset NCL, leading to abnormal palmitoylation and lipofuscin deposits.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Editorial Material
Clinical Neurology
Ajith Cherian, K. P. Divya, Naveen Kumar Paramasivan, Syam Krishnan
Summary: Kufs disease, a type of adult neuronal ceroid lipofuscinosis, differs from childhood forms in its late onset and preserved vision. It is subclassified into type A, characterized by progressive myoclonus epilepsy, and type B, characterized by dementia with motor involvement.
Article
Biochemistry & Molecular Biology
Kei Takahashi, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
Summary: This study characterized the retinal phenotype in mature PGRN knockout mice, showing reduced a-wave amplitude and outer nuclear thickness in Grn(-/-) mice compared to wild-type mice. Increased accumulation of retinal microglial cells on the RPE apical layer and changes in lysosomal protein expression were observed in Grn(-/-) mice, indicating a potential modulation of microglial dynamics in PGRN deficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Magdalena Badura-Stronka, Anna Winczewska-Wiktor, Anna Pietrzak, Adam Sebastian Hirschfeld, Tomasz Zemojtel, Katarzyna Wolynska, Katarzyna Bednarek-Rajewska, Monika Seget-Dubaniewicz, Agnieszka Matheisel, Anna Latos-Bielenska, Barbara Steinborn
Summary: Mutations in the CLN8 gene can cause late-infantile neuronal ceroid lipofuscinosis (LINCL), and a novel CLN8 mutation was identified in a female pediatric patient. This case highlights the presence of a continuous spectrum of CLN8-associated phenotypes.
Review
Cell Biology
Marcel Klein, Guido Hermey
Summary: Evidence from genetics and cellular and animal models suggests a link between early and late neurodegenerative disorders. This review summarizes the connection between Alzheimer's disease and neuronal ceroid lipofuscinoses. Genetic studies have found overlapping mutations between clinically diagnosed Alzheimer's and neuronal ceroid lipofuscinoses. Dysfunctions in intracellular trafficking mechanisms and the autophagy-endolysosome system are believed to be shared cytopathological processes. Understanding these common mechanisms is important for finding therapeutic targets and tailored treatments.
NEURAL REGENERATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Corina-Marcela Rus, Daniel L. Polla, Sebastiano Di Bucchianico, Steffen Fischer, Joerg Hartkamp, Guido Hartmann, Yunus Alpagu, Claudia Cozma, Ralf Zimmermann, Peter Bauer
Summary: This study analyzed the metabolic changes in CLN6 disease patients and identified potential biomarkers for diagnosis and disease monitoring. The most impacted metabolic profile was associated with sphingolipids, glycerophospholipids metabolism, and calcium signaling. Fifteen metabolites were found to be significantly different between disease and control groups, and they were downregulated in the disease group.
SCIENTIFIC REPORTS
(2023)
Article
Veterinary Sciences
Shinji Tamura, Masaya Tsuboi, Naotami Ueoka, Shoko Doi, Yumiko Tamura, Kazuyuki Uchida, Akira Yabuki, Osamu Yamato
Summary: This case study presents a male Shikoku Inu diagnosed with adult-onset neuronal ceroid lipofuscinosis, characterized by progressive gait abnormality, neurological deficits, and visual impairments. Pathologically, there were pigment deposits and membranous material accumulation in the neurons.
VETERINARY SCIENCES
(2021)
Review
Clinical Neurology
Keigo Takahashi, Hemanth R. Nelvagal, Jenny Lange, Jonathan D. Cooper
Summary: This article summarizes the latest understanding of glial pathologies and their contribution to the pathogenesis of NCLs, highlighting the challenges that require further research.
FRONTIERS IN NEUROLOGY
(2022)
Letter
Genetics & Heredity
Thouraya Ben Younes, Ichraf Kraoua, Sarah Snanoudj, Hedia Klaa, Hanene Benrhouma, Aida Rouissi, Catherine Caillaud, Myriam Chaabouni, Najoua Miladi, Soumeya Bekri, Ilhem Ben Youssef-Turki
Summary: This study involved 13 patients diagnosed with neuronal ceroid lipofuscinosis, which is a group of rare genetically-determined neurodegenerative diseases characterized by clinical and genetic heterogeneity. Brain MRI and electroencephalogram aid in diagnosis.
Review
Biochemistry & Molecular Biology
Konrad Kaminiow, Sylwia Kozak, Justyna Paprocka
Summary: Neuronal ceroid lipofuscinoses (NCLs) are rare neurodegenerative disorders that affect children and adults. They are classified based on shared clinical symptoms and pathology. Thirteen autosomal recessive gene variants and one autosomal dominant gene variant have been identified in NCL. Symptoms of NCL include vision loss, mental and motor deterioration, and seizures.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Robert J. J. Huber
Summary: Ceroid lipofuscinosis neuronal (CLN) genes encode 13 proteins that play a role in regulating cellular processes in the endomembrane system. Mutations in CLN genes cause neuronal ceroid lipofuscinosis (NCL), a severe neurodegenerative disease. This review summarizes the current understanding of CLN gene and protein networking in mammalian cells, with a focus on identifying new molecular targets for therapy development. Interestingly, CLN genes and proteins have also been linked to other forms of neurodegeneration, such as Alzheimer's disease and Parkinson's disease, suggesting potential insights into related diseases.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Ahmed Morsy, Angelica Carmona, Paul C. Trippier
Summary: Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare fatal inherited neurodegenerative lysosomal storage disorders for which no curative treatments are currently available. Induced pluripotent stem cells (iPSCs) can serve as valuable models to shed light on disease mechanisms and facilitate drug discovery for NCL.
Review
Neurosciences
Sara Bernardi, Federica Gemignani, Maria Marchese
Summary: Progressive myoclonic epilepsies (PMEs) are rare neurodegenerative diseases characterized by myoclonus, seizures, and neurological deterioration. The involvement of the cerebellar cortex and the loss of Purkinje cells (PCs) in PMEs are associated with motor impairments and epilepsy. This review focuses on the role of PCs in epilepsy and particularly highlights their involvement in seizure phenotype in neuronal ceroid lipofuscinosis (NCL).
NEUROBIOLOGY OF DISEASE
(2023)
Article
Pharmacology & Pharmacy
Fatima Bilal, Anne Montfort, Julia Gilhodes, Virginie Garcia, Joelle Riond, Stephane Carpentier, Thomas Filleron, Celine Colacios, Thierry Levade, Ahmad Daher, Nicolas Meyer, Nathalie Andrieu-Abadie, Bruno Segui
FRONTIERS IN PHARMACOLOGY
(2019)
Article
Multidisciplinary Sciences
Caroline Imbert, Anne Montfort, Marine Fraisse, Elie Marcheteau, Julia Gilhodes, Elodie Martin, Florie Bertrand, Marlene Marcellin, Odile Burlet-Schiltz, Anne Gonzalez de Peredo, Virginie Garcia, Stephane Carpentier, Sophie Tartare-Deckert, Pierre Brousset, Philippe Rochaix, Florent Puisset, Thomas Filleron, Nicolas Meyer, Laurence Lamant, Thierry Levade, Bruno Segui, Nathalie Andrieu-Abadie, Celine Colacios
NATURE COMMUNICATIONS
(2020)
Review
Oncology
Patricia Dubot, Leonardo Astudillo, Nicole Therville, Frederique Sabourdy, Jerome Stirnemann, Thierry Levade, Nathalie Andrieu-Abadie
Review
Cell Biology
Lorry Carrie, Mathieu Virazels, Carine Dufau, Anne Montfort, Thierry Levade, Bruno Segui, Nathalie Andrieu-Abadie
Article
Oncology
Anne Montfort, Thomas Filleron, Mathieu Virazels, Carine Dufau, Jean Milhes, Cecile Pages, Pascale Olivier, Maha Ayyoub, Muriel Mounier, Amelie Lusque, Stephanie Brayer, Jean-Pierre Delord, Nathalie Andrieu-Abadie, Thierry Levade, Celine Colacios, Bruno Segui, Nicolas Meyer
Summary: TNF blockers can help manage gastrointestinal inflammatory side effects following nivolumab and/or ipilimumab treatment in patients with advanced melanoma, and may enhance the efficacy of immune checkpoint inhibitors. The combination of certolizumab showed a high response rate in patients, warranting further investigation. Both combinations were found to be safe and showed clinical and biological activities in human patients.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Anne Montfort, Florie Bertrand, Julia Rochotte, Julia Gilhodes, Thomas Filleron, Jean Milhes, Carine Dufau, Caroline Imbert, Joelle Riond, Marie Tosolini, Christopher J. Clarke, Florent Dufour, Andrei A. Constantinescu, Nilton De Franca Junior, Virginie Garcia, Michel Record, Pierre Cordelier, Pierre Brousset, Philippe Rochaix, Sandrine Silvente-Poirot, Nicole Therville, Nathalie Andrieu-Abadie, Thierry Levade, Yusuf A. Hannun, Herve Benoist, Nicolas Meyer, Olivier Micheau, Celine Colacios, Bruno Segui
Summary: Dysregulation of lipid metabolism affects cancer cell behavior, and increasing SMPD3 expression can reduce melanoma growth and enhance Th1 polarization and CD8(+) T-cell-dependent immune responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Celia Cintas, Thibault Douche, Zahra Dantes, Emmanuelle Mouton-Barbosa, Marie-Pierre Bousquet, Coralie Cayron, Nicole Therville, Frederic Pont, Fernanda Ramos-Delgado, Camille Guyon, Barbara Garmy-Susini, Paola Cappello, Odile Burlet-Schiltz, Emilio Hirsch, Anne Gomez-Brouchet, Benoit Thibault, Maximilian Reichert, Julie Guillermet-Guibert
Summary: The PI3K pathway is highly active in human cancers and its inhibition is a potential therapeutic strategy for pancreatic cancer. However, different isoform-selective PI3K inhibitors have varying effects, with some leading to reactivation of downstream signaling. Combining inhibitors with different isoform selectivity may prevent the induction of compensatory signals and have a synergistic effect on cell survival.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Dermatology
Ikrame Lazar, Emily Clement, Lorry Carrie, David Esteve, Stephanie Dauvillier, Mohamed Moutahir, Stephane Dalle, Veronique Delmas, Nathalie Andrieu-Abadie, Lionel Larue, Catherine Muller, Laurence Nieto
Summary: Obesity is associated with the occurrence and development of melanoma. The mechanism involves the downregulation of p16(INK4A) expression in melanoma cells by adipocytes through beta-catenin-dependent regulation, which increases cell motility. Adipocytes from individuals with obesity secrete a larger number of vesicles, delivering more beta-catenin to melanoma cells.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Oncology
Patricia Dubot, Leonardo Astudillo, Nicole Therville, Lorry Carrie, Magali Pettazzoni, David Cheillan, Jerome Stirnemann, Thierry Levade, Nathalie Andrieu-Abadie, Frederique Sabourdy
Summary: Inherited disorders of lipid metabolism, known as sphingolipidoses, are associated with an increased occurrence of cancer. This study explores the potential involvement of lysosphingolipids, the deacylated derivatives of sphingolipids, in cancer development through reviewing literature and presenting original findings on melanoma cells. Further investigations are needed to understand the role of these lipids in sphingolipidoses and malignant diseases.
Review
Oncology
Laurence Pellerin, Lorry Carrie, Carine Dufau, Laurence Nieto, Bruno Segui, Thierry Levade, Joelle Riond, Nathalie Andrieu-Abadie
Article
Chemistry, Organic
Tessa Castellan, Virginie Garcia, Frederic Rodriguez, Isabelle Fabing, Yevhenii Shchukin, My Lan Tran, Stephanie Ballereau, Thierry Levade, Yves Genisson, Cecile Dehoux
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
G. F. Senguel, R. Mishra, E. Candiello, P. Schu
Summary: AP2 forms AP2 CCV with clathrin and other coat proteins, and synapses contain different types of CCV. The stability and composition of CCV are regulated by various factors, including Hsc70 and phosphorylation patterns. The knockout of the AP1/O1B complex disrupts synaptic vesicle recycling and endosomal protein sorting, leading to upregulation of endocytosis. Stable CCV, termed stCCV, have distinct characteristics and specialized functions in synaptic plasticity. The phosphorylation of Hsc70 and the levels of kinases play a crucial role in regulating the stability and disassembly of clathrin in CCV.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Martin Fluck, Colline Sanchez, Vincent Jacquemond, Christine Berthier, Marie-Noelle Giraud, Daniel Jacko, Kathe Bersiner, Sebastian Gehlert, Guus Baan, Richard T. Jaspers
Summary: Enhancing CaMKII signaling improves fatigue resistance and contractile characteristics of skeletal muscle by enhancing calcium release.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Letter
Biochemistry & Molecular Biology
Federica Coppola, Sara Monaci, Alessandro Falsini, Carlo Aldinucci, Irene Filippi, Daniela Rossi, Fabio Carraro, Antonella Naldini
Summary: The adaptor protein p62 plays a crucial role in maintaining the survival of dendritic cells (DCs) under hypoxic conditions by preserving Erk1/2 phosphorylation and reducing AMPK activation, thus extending their lifespan to ensure their functions in hypoxic microenvironments.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Jenifer Pendiuk Goncalves, Jorvani Cruz Villarreal, Sierra A. Walker, Xuan Ning Sharon Tan, Chad Borges, Joy Wolfram
Summary: This study used a mass spectrometry-based approach to assess the differences in glycan features between extracellular vesicles (EVs) and originating cells. The results showed that EVs selectively enriched specific glycan features, particularly those associated with binding to the extracellular matrix. The study also found differences in EV glycan sorting between different metastatic cell lines and mouse models, indicating a potential role of glycan diversity in the metastatic process.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
De-ao Gong, Peng Zhou, Wen-yi Chang, Jia-yao Yang, Yan-lai Zhang, Ai-long Huang, Ni Tang, Kai Wang
Summary: Liver cancer, ranked sixth globally, is a major contributor to cancer-related mortality. Metastasis is the main cause of treatment failure and deaths in liver cancer. The SPOP-CREB5-MET axis plays a significant role in liver cancer metastasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ning Huang, Jun Tang, Xiaoyao Yi, Maoxin Zhang, Bin Li, Yuan Cheng, Jin Chen
Summary: This study reveals that glioma-derived S100A9 can induce microglial M2 polarization, inhibit CD8+ T lymphocytes, and promote immunosuppression. The mechanism is related to the interaction with alpha v133 integrin and subsequent activation of AKT1 in microglia. The expression of S100A9 is positively associated with CD206 expression and negatively correlated with CD8+ T lymphocyte accumulation in the TME, suggesting a potential role of S100A9 in regulating the tumor microenvironment and immune evasion in glioma.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Yomna S. Abd El-Aziz, Matthew J. McKay, Mark P. Molloy, Betty McDowell, Elizabeth Moon, Loretta Sioson, Amy Sheen, Angela Chou, Anthony J. Gill, Patric J. Jansson, Sumit Sahni
Summary: This study identified a novel combination of autophagy inhibitors that can effectively inhibit the proliferation of oral squamous cell carcinoma (OSCC) cells, including both chemosensitive and chemoresistant cells. This research is important for the development of new therapies for advanced OSCC tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Luojia Liu, Xiaoqiang Liu, Ying Chen, Meng Kong, Jinghong Zhang, Min Jiang, Hongling Zhou, Jinrui Yang, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jiaping Zhang
Summary: Our study revealed that the Paxillin/HDAC6 signaling pathway regulates microtubule acetylation in electric field-guided keratinocyte migration.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Soren Abel, Frank Sobott, J. Preben Morth
Summary: The study reveals the complex interaction between bacterial magnesium transporter A (MgtA) and cardiolipin 18:1 and cardiolipin 16:0, highlighting the importance of lipid environment in protein activity and stability. Further understanding of Mg2+ homeostasis in bacteria will provide insights into bacterial infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Sumit Kinger, Yuvraj Anandrao Jagtap, Ankur Rakesh Dubey, Prashant Kumar, Akash Choudhary, Rohan Dhiman, Vijay Kumar Prajapati, Deepak Chitkara, Krishna Mohan Poluri, Amit Mishra
Summary: Efficient protein synthesis and quality control mechanisms are crucial for maintaining proteostasis and preventing neurodegeneration. This study demonstrates that treating cells with Lanosterol can enhance the proteolytic activity of Proteasome and promote the removal of misfolded proteins, suggesting a potential therapeutic approach for abnormal protein accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Karolina Stepien, Adrianna Skoneczna, Monika Kula-Maximenko, Lukasz Jurczyk, Mateusz Molon
Summary: The replication of DNA requires a complex machinery called the replisome, which is highly conserved across species. One crucial component of the replisome is the CMG helicase complex, which unwinds DNA and coordinates the assembly and function of other replisome components. In this study, the impact of the absence of one copy of the CMG complex genes on the physiology and aging of yeast cells was investigated. The findings showed disruptions in the cell cycle, extended doubling times, and alterations in the biochemical profile of these cells. Importantly, it was found that heterozygous cells for CMG helicase genes exhibited increased reproductive potential and delayed aging. The study also highlighted potential therapeutic targets for cancer treatment using yeast.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Nishadh Rathod, Guadalupe Guerrero-Serna, Howard S. Young, L. Michel Espinoza-Fonseca
Summary: This study reveals that replacing Lys27 with Asn enhances the inhibitory potency of MLN without affecting SERCA's affinity for Ca2+. The findings suggest that the SERCA site modulating Ca2+ affinity also functions as a catalytic activity switch.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Can Jiang, Chunyang Zhang, Min Dai, Fuyan Wang, Sa Xu, Dan Han, Yanyan Wang, Yajie Cao, Yanyan Liang, Ziyu Zhang, Lina Yan, Yujun Shen, Kewu He, Yuxian Shen, Jun Liu
Summary: The phosphorylation of p65 and the expression of SUMO1 are increased in cancer tissues of HCC patients, and there is a positive correlation between SUMO1 and phosphorylated p65. SUMOylation of p65 by SUMO1 promotes p65 nuclear import and enhances NF-xB activity. Both SUMOylation and phosphorylation of p65 increase the viability and invasion of hepatoma cells, and decrease cell apoptosis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ming-Fo Hsu, Yoshihiro Ito, Jai Prakash Singh, Shu-Fang Hsu, Alan Wells, Kuang-Yu Jen, Tzu-Ching Meng, Fawaz G. Haj
Summary: This study identified alpha-actinin4 as a novel substrate of PTP1B in podocytes and demonstrated their interaction in regulating podocyte function. Targeting PTP1B and alpha-actinin4 could be a potential therapeutic approach for podocyte injury.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Paulo F. V. Bizerra, Eduardo H. Gilglioni, Hang Lam Li, Simei Go, Ronald P. J. Oude Elferink, Arthur J. Verhoeven, Jung -Chin Chang
Summary: This study investigates the role of cyclic AMP (cAMP) in glycogen metabolism and reveals that cAMP regulates glycogenolysis in opposite directions depending on its site of synthesis within cells and downstream effectors. The canonical tmAC-cAMP-PKA signaling promotes glycogenolysis, while the non-canonical sAC-cAMP-Epac1 signaling suppresses glycogenolysis. This highlights the importance of cAMP microdomain organization for distinct metabolic regulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)