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
Endocrinology & Metabolism
Avisek Mondal, Abhilash P. Appu, Tamal Sadhukhan, Maria B. Bagh, Rafael M. Previde, Sriparna Sadhukhan, Stanko Stojilkovic, Aiyi Liu, Anil B. Mukherjee
Summary: This study reveals a previously unknown role of Ppt1 in regulating lysosomal calcium homeostasis and suggests that this defect may contribute to the pathogenesis of CLN1 disease.
JOURNAL OF INHERITED METABOLIC DISEASE
(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.
Article
Genetics & Heredity
J. Schaefers, L. J. van der Giessen, C. Klees, E. H. Jacobs, S. Sieverdink, M. H. G. Dremmen, J. K. H. Spoor, A. T. van der Ploeg, J. M. P. van den Hout, H. H. Huidekoper
Summary: Research shows that intracerebroventricular enzyme replacement therapy can delay the onset of symptoms in presymptomatic patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), advocating for early treatment initiation before symptom onset in larger cohort studies.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
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
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
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)
Article
Neurosciences
Yoshiko Munesue, Naohide Ageyama, Nobuyuki Kimura, Ichiro Takahashi, Shunya Nakayama, Sachi Okabayashi, Yuko Katakai, Hiroshi Koie, Ken-ichi Yagami, Kazuhiro Ishii, Akira Tamaoka, Yasuhiro Yasutomi, Nobuhiro Shimozawa
Summary: We report the discovery of cynomolgus macaques carrying the CLN2/TPP1 variant and confirm their neurodegenerative symptoms, which could serve as a new non-human primate model for NCL type 2 disease. These macaques exhibited progressive neuronal clinical symptoms and showed significant cerebellar and cerebral atrophy in the gray matter. Histopathological analysis revealed severe neuronal loss and degeneration, as well as the presence of ceroid-lipofuscin in neurons.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
Parisa Lotfi, Dennis Y. Tse, Alberto Di Ronza, Michelle L. Seymour, Giuseppe Martano, Jonathan D. Cooper, Fred A. Pereira, Maria Passafaro, Samuel M. Wu, Marco Sardiello
Article
Biochemistry & Molecular Biology
Natalia Niemir, Laura Rouviere, Aurore Besse, Marie T. Vanier, Jasmin Dmytrus, Thibaut Marais, Stephanie Astord, Jean-Philippe Puech, Ganna Panasyuk, Jonathan D. Cooper, Martine Barkats, Catherine Caillaud
HUMAN MOLECULAR GENETICS
(2018)
Article
Biochemistry & Molecular Biology
Giulia Massaro, Citra N. Z. Mattar, Andrew M. S. Wong, Ernestas Sirka, Suzanne M. K. Buckley, Bronwen R. Herbert, Stefan Karlsson, Dany P. Perocheau, Derek Burke, Simon Heales, Angela Richard-Londt, Sebastian Brandner, Mylene Huebecker, David A. Priestman, Frances M. Platt, Kevin Mills, Arijit Biswas, Jonathan D. Cooper, Jerry K. Y. Chan, Seng H. Cheng, Simon N. Waddington, Ahad A. Rahim
Review
Clinical Neurology
Steven E. Arnold, Zoe Arvanitakis, Shannon L. Macauley-Rambach, Aaron M. Koenig, Hoau-Yan Wang, Rexford S. Ahima, Suzanne Craft, Sam Gandy, Christoph Buettner, Luke E. Stoeckel, David M. Holtzman, David M. Nathan
NATURE REVIEWS NEUROLOGY
(2018)
Review
Clinical Neurology
Sara E. Mole, Glenn Anderson, Heather A. Band, Samuel F. Berkovic, Jonathan D. Cooper, Sophia-Martha Kleine Holthaus, Tristan R. Mckay, Diego L. Medina, Ahad A. Rahim, Angela Schulz, Alexander J. Smith
Article
Hematology
Alexander C. Bashore, Mingxia Liu, Chia-Chi C. Key, Elena Boudyguina, Xianfeng Wang, Caitlin M. Carroll, Janet K. Sawyer, Adam E. Mullick, Richard G. Lee, Shannon L. Macauley, John S. Parks
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2019)
Article
Multidisciplinary Sciences
S. L. Eaton, C. Proudfoot, S. G. Lillico, P. Skehe, R. A. Kline, K. Hamer, N. M. Rzechorzek, E. Clutton, R. Gregson, T. King, C. A. O'Neill, J. D. Cooper, G. Thompson, C. B. Whitelaw, T. M. Wishart
SCIENTIFIC REPORTS
(2019)
Review
Geriatrics & Gerontology
Caitlin M. Carroll, Shannon L. Macauley
FRONTIERS IN AGING NEUROSCIENCE
(2019)
Article
Neurosciences
Kylie Kavanagh, Stephen M. Day, Morgan C. Pait, William R. Mortiz, Christopher B. Newgard, Olga Ilkayeva, Donald A. Mcclain, Shannon L. Macauley
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Naresh Damuka, Paul W. Czoty, Ashley T. Davis, Michael A. Nader, Susan H. Nader, Suzanne Craft, Shannon L. Macauley, Lindsey K. Galbo, Phillip M. Epperly, Christopher T. Whitlow, April T. Davenport, Thomas J. Martin, James B. Daunais, Akiva Mintz, Kiran Kumar Solingapuram Sai
Editorial Material
Biochemistry & Molecular Biology
Erin M. Gibson, F. Chris Bennett, Shawn M. Gillespie, Ali Deniz Guler, David H. Gutmann, Casey H. Halpern, Sarah C. Kucenas, Clete A. Kushida, Mackenzie Lemieux, Shane Liddelow, Shannon L. Macauley, Qingyun Li, Matthew A. Quinn, Laura Weiss Roberts, Naresha Saligrama, Kathryn R. Taylor, Humsa S. Venkatesh, Belgin Yalcin, J. Bradley Zuchero
Article
Clinical Neurology
H. R. Nelvagal, J. T. Dearborn, J. R. Ostergaard, M. S. Sands, J. D. Cooper
Summary: This study investigated the early pathology of CLN1 disease in the spinal cord of Ppt1-deficient mice, revealing significant microglial activation at 1 month, followed by astrocytosis and other changes at 2 months, and accumulation of storage material and lymphocyte infiltration at 3 months. Inflammatory cytokine expression was altered as early as one month. Behavioral abnormalities were observed at 2 months before a decline in overall locomotor performance. Early onset of the disease 2 months earlier than expected indicates the need for therapies during the presymptomatic period.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Review
Zoology
Brett M. Frye, Suzanne Craft, Caitlin S. Latimer, C. Dirk Keene, Thomas J. Montine, Thomas C. Register, Miranda E. Orr, Kylie Kavanagh, Shannon L. Macauley, Carol A. Shively
Summary: The study highlights the vervet monkey as a suitable model for age-related Alzheimer's disease, with traits related to cognitive function, physical function, glucose handling, and more. Evidence suggests that aging vervets exhibit characteristics consistent with early AD, making them a valuable model for LOAD research. Studies show relationships between AD-like neuropathology in vervets and modifiable risk factors, shaping future research to understand mechanisms underlying divergent neurocognitive aging trajectories and develop interventions for LOAD.
AMERICAN JOURNAL OF PRIMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Joshua T. Dearborn, Hemanth R. Nelvagal, Nicholas R. Rensing, Keigo Takahashi, Stephanie M. Hughes, Thomas M. Wishart, Jonathan D. Cooper, Michael Wong, Mark S. Sands
Summary: In a mouse model of CLN1 disease, chronic CBD administration reduced neuroinflammation but had no apparent effect on seizures and neuron survival. Higher doses of CBD may be needed to reduce neurodegeneration and seizure frequency.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Samantha L. Eaton, Fraser Murdoch, Nina M. Rzechorzek, Gerard Thompson, Claudia Hartley, Benjamin Thomas Blacklock, Chris Proudfoot, Simon G. Lillico, Peter Tennant, Adrian Ritchie, James Nixon, Paul M. Brennan, Stefano Guido, Nadia L. Mitchell, David N. Palmer, C. Bruce A. Whitelaw, Jonathan D. Cooper, Thomas M. Wishart
Summary: The impact of neurological disorders is globally recognized, and the translation from rodent-derived therapeutics to human neurological interventions is challenging. In order to improve translation, higher order mammals with complex neuroanatomy, such as livestock, are being used. We provide comprehensive neurological assessment protocols for large animal species to standardize the characterization of these models and recommend their use in neurological clinical scoring.