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)
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.
Letter
Dermatology
Akari Sakai, Satoru Shinkuma, Nobuaki Miura, Tokiko Deguchi, Mahoko Oginezawa, Mami Nakajima, Tatsuya Katsumi, Ryota Hayashi, Riichiro Abe
Summary: This article describes a case of Papillon-Lefevre syndrome in a patient with a novel p.G430V and recurrent p.G301S missense mutation, showing aggravated skin lesions in wintertime. A temperature-dependent cathepsin C enzymatic activity study suggests a possible association between seasonal fluctuations, minimal dental involvement, and temperature.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Clinical Neurology
Mette Moller Handrup, Henning Molgaard, Brian N. Andersen, John R. Ostergaard
Summary: The article "Translation: The use of pacemaker treatment in Juvenile Neuronal Ceroid Lipofuscinosis" introduces the application of pacemaker treatment for patients with Juvenile Neuronal Ceroid Lipofuscinosis and conducts a follow-up study on the original Danish CLN3-heart population, indicating that pacemaker treatment has a significant impact on the quality of life of patients.
FRONTIERS IN NEUROLOGY
(2022)
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.
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)
Article
Immunology
Giulia Melo Lettieri, Luander Medrado Santiago, Giancarlo Crosara Lettieri, Luiz Gustavo dos Anjos Borges, Leticia Marconatto, Laudimar Alves de Oliveira, Naile Dame-Teixeira, Loise Pedrosa Salles
Summary: This study characterized the oral phenotype and salivary microbiome of three sisters with Papillon-Lefevre syndrome (PLS). The main phenotypic characteristics of PLS were bone loss and premature tooth loss. They all presented hyposalivation, but the salivary microbiota differed among the sisters.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
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
Clinical Neurology
Ilknur Surucu Kara, Engin Kose, Neslihan Dogulu, Merve Feyza Yuksel, Serdar Ceylaner, Tanil Kendirli, Fatma Tuba Eminoglu
Summary: Neuronal ceroid lipofuscinosis (CLN) 7 is a neurodegenerative disease characterized by motor and cognitive decline, seizures, and vision loss. Atypical manifestations such as ataxia and autistic behaviors have also been reported. This case report highlights the importance of considering CLN7 in cases with similar clinical findings and choreo-athetotic movements. Treatment of septic shock led to improvement of symptoms.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Clinical Neurology
Giancarlo Todiere, Stefania Della Vecchia, Maria Aurora Morales, Andrea Barison, Ivana Ricca, Alessandra Tessa, Elisa Colombi, Filippo Maria Santorelli
Summary: Cardiac MRI is essential for diagnosing hypertrophic cardiomyopathy and may play a role in neuronal ceroid lipofuscinosis, allowing for early diagnosis and treatment monitoring.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Emily Gardner, Sara E. Mole
Summary: Neuronal ceroid lipofuscinoses are a group of inherited neurodegenerative disorders affecting children and adults, sharing similar clinical features and accumulation of storage material. Over 530 mutations have been identified in 13 genes, encoding various proteins including lysosomal enzymes. While many mutations are associated with typical disease phenotypes, there is an increasing description of variant disease phenotypes.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sudarshan R. Malla, Burkhard Krueger, Thomas Wartmann, Matthias Sendler, Ujjwal M. Mahajan, F. Ulrich Weiss, Franziska G. Thiel, Carina De Boni, Fred S. Gorelick, Walter Halangk, Ali A. Aghdassi, Thomas Reinheckel, Anna S. Gukovskaya, Markus M. Lerch, Julia Mayerle
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Simona Capponi, Nadja Stoeffler, Manuel Irimia, Frederik M. A. Van Schaik, Mercedes M. Ondik, Martin L. Biniossek, Lisa Lehmann, Julia Mitschke, Marit W. Vermunt, Menno P. Creyghton, Ann M. Graybiel, Thomas Reinheckel, Oliver Schilling, Benjamin J. Blencowe, Jill R. Crittenden, H. Th Marc Timmers
Article
Multidisciplinary Sciences
Saara Hamalisto, Jonathan Lucien Stahl, Elena Favaro, Qing Yang, Bin Liu, Line Christoffersen, Ben Loos, Claudia Guasch Boldu, Johanna A. Joyce, Thomas Reinheckel, Marin Barisic, Marja Jaattela
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Alejandro Gomez-Auli, Larissa Elisabeth Hillebrand, Daniel Christen, Sira Carolin Guenther, Martin Lothar Biniossek, Christoph Peters, Oliver Schilling, Thomas Reinheckel
Summary: The study investigates cathepsin B-mediated secretome changes in breast cancer and highlights CREG1 as a key factor in the tumor microenvironment that can suppress malignant cell behavior.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nezka Kavcic, Miha Butinar, Barbara Sobotic, Marusa Hafner Cesen, Ana Petelin, Lea Bojic, Tina Zavasnik Bergant, Andreja Bratovs, Thomas Reinheckel, Boris Turk
Review
Biochemistry & Molecular Biology
Lena Hoelzen, Maria Alejandra Parigiani, Thomas Reinheckel
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2020)
Article
Immunology
Junjun Ni, Juan Zhao, Xinwen Zhang, Thomas Reinheckel, Vito Turk, Hiroshi Nakanishi
Summary: The study found that Cathepsin H plays a critical role in the proteolytic maturation and stabilization of TLR3, which is necessary for IFN-beta production. CatH deficiency led to impaired TLR3/IFN-beta signaling, resulting in microglial cell death and astrogliosis/glial scar formation in the hippocampus following HI injury, thereby suppressing hippocampal atrophy.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Tingting Zhang, Huan Du, Mariela Nunez Santos, Xiaochun Wu, Mitchell D. Pagan, Lianne Jillian Trigiani, Nozomi Nishimura, Thomas Reinheckel, Fenghua Hu
Summary: This study generated and characterized antibodies specific to each granulin peptide and found that the levels of individual granulin peptides are differently regulated in different tissues. The study also revealed variations in the levels of PGRN and granulin peptides in different brain regions, and showed that the changes in granulin A corresponded to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and prosaposin affected the ratios between individual granulin peptides.
MOLECULAR NEURODEGENERATION
(2022)
Review
Biochemistry & Molecular Biology
Thomas Reinheckel, Martina Tholen
Summary: For a long time, lysosomes were considered as organelles responsible for garbage disposal within the cell. Recent research, however, has shown that lysosomes also play a crucial role in integrating intracellular and extracellular signals. It has been found that lysosomal enzymes can be released in a way that is compatible with cellular survival, challenging the previous belief that impaired lysosomal membrane integrity leads to cell death. This review discusses the evidence and mechanisms by which lysosomal enzymes, particularly cathepsin proteases, reach unusual destinations within the cell.
Review
Pharmacology & Pharmacy
Gregory Hook, Thomas Reinheckel, Junjun Ni, Zhou Wu, Mark Kindy, Christoph Peters, Vivian Hook
Summary: This review evaluates the effects of deleting the CTSB gene on brain dysfunctions in neurological diseases and aging animal models. The findings suggest that CTSB gene knockout improves behavioral deficits, neuropathology, and biomarkers, supporting CTSB as a rational drug target for treating neurologic disorders.
PHARMACOLOGICAL REVIEWS
(2022)
Article
Oncology
Lena Hoelzen, Kerstin Syre, Jan Mitschke, Tilman Brummer, Cornelius Miething, Thomas Reinheckel
Summary: This article investigates the role of proteases in breast cancer progression and metastasis. By using genetic screens, the authors identify 252 protease genes involved in breast cancer cell growth, with 9 genes functionally validated. The study also reveals that environmental conditions influence breast cancer cell dependency on certain proteases.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emilia Neuwirt, Giovanni Magnani, Tamara Cikovic, Svenja Woehrle, Larissa Fischer, Anna Kostina, Stephan Flemming, Nora J. Fischenich, Benedikt S. Saller, Oliver Gorka, Steffen Renner, Claudia Agarinis, Christian N. Parker, Andreas Boettcher, Christopher J. Farady, Rebecca Kesselring, Christopher Berlin, Rolf Backofen, Marta Rodriguez-Franco, Clemens Kreutz, Marco Prinz, Martina Tholen, Thomas Reinheckel, Thomas Ott, Christina J. Gross, Philipp J. Jost, Olaf Gross
Summary: The activation mechanisms of NOD-like receptor (NLR) protein-mediated inflammasomes were investigated. It was discovered that tyrosine kinase inhibitors (TKIs), including clinically approved drugs like imatinib and crizotinib, activated the NLRP3 inflammasome. These TKIs caused lysosomal swelling and damage, resulting in cell lysis and activation of NLRP3. This finding suggests a potential off-target effect of TKIs that may contribute to their clinical efficacy or adverse effects.
Article
Multidisciplinary Sciences
Claudio Bussi, Tiaan Heunis, Enrica Pellegrino, Elliott M. Bernard, Nourdine Bah, Mariana Silva Dos Santos, Pierre Santucci, Beren Aylan, Angela Rodgers, Antony Fearns, Julia Mitschke, Christopher Moore, James MacRae, Maria Greco, Thomas Reinheckel, Matthias Trost, Maximiliano G. Gutierrez
Summary: This study reveals that limited lysosomal damage leads to changes in the mitochondrial proteome and the modulation of macrophage immunometabolism. It shows that protease leakage from lysosomes triggers a cell death-independent proteolytic remodeling of the mitochondrial proteome in macrophages.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Lena Hoelzen, Jan Mitschke, Claudia Schoenichen, Maria Elena Hess, Sophia Ehrenfeld, Melanie Boerries, Cornelius Miething, Tilman Brummer, Thomas Reinheckel
Summary: This study suggests that proteases can act synergistically with PI3K inhibition in breast cancer cells, leading to enhanced therapeutic outcomes. Through a series of experiments, the researchers identified Usp7, Metap1, and Metap2 as key proteases that exhibit synthetic lethal effects when combined with PI3K inhibitors.
Article
Medicine, Research & Experimental
Lindsay B. Alcaraz, Aude Mallavialle, Timothee David, Danielle Derocq, Frederic Delolme, Cindy Dieryckx, Caroline Mollevi, Florence Boissiere-Michot, Joelle Simony-Lafontaine, Stanislas Du Manoir, Pitter F. Huesgen, Christopher M. Overall, Sophie Tartare-Deckert, William Jacot, Thierry Chardes, Severine Guiu, Pascal Roger, Thomas Reinheckel, Catherine Moali, Emmanuelle Liaudet-Coopman
Summary: This study identified a novel crosstalk between proteases and matricellular proteins in the tumor microenvironment through limited SPARC proteolysis, revealing a novel targetable 9-kDa bioactive SPARC fragment for new TNBC treatments. The research paves the way for developing strategies to target bioactive fragments from matricellular proteins in TNBC.