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)
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
Psychiatry
John R. R. Ostergaard
Summary: This study addresses the neurobiological mechanisms of anxiety and anxious behavior in juvenile neuronal ceroid lipofuscinosis (JNCL) patients. During the terminal phase, JNCL patients experience an increase in anxious behavior which is different from the earlier stages. The study suggests that the anxious behavior observed in these patients may be a developmental natural fear-response similar to what is seen in children aged 0-2 years. Additionally, JNCL patients in the terminal phase exhibit autonomic imbalance, characterized by sympathetic hyperactivity, leading to phenotypically similar symptoms as Paroxysmal Sympathetic Hyperactivity. Treatment options, such as sedatives and minimizing stimuli, are currently limited and further investigation is required.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Cell Biology
Vicki J. Swier, Katherine A. White, Tyler B. Johnson, Xiaojun Wang, Jimin Han, David A. Pearce, Ruchira Singh, Arlene V. Drack, Wanda Pfeifer, Christopher S. Rogers, Jon J. Brudvig, Jill M. Weimer
Summary: This study presents a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, showing consistent pathology and behavioral impairment mirroring clinical presentation. The model demonstrates its value in studying the role of CLN3 and safety/efficacy of novel disease-modifying therapeutics.
DISEASE MODELS & MECHANISMS
(2023)
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)
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)
Review
Clinical Neurology
John R. Ostergaard
Summary: This study discusses a rational approach to prevent and/or treat non-epileptic episodes in patients with juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3 disease). Based on the knowledge of triggering factors and the impact of CLN3 disease on neural anxiety/fear circuit, the study suggests increasing the threshold of discomfort impact, modulating the imbalance of central network inhibition and excitation, and restoring the balance between sympathetic and parasympathetic neural systems.
FRONTIERS IN NEUROLOGY
(2023)
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)
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
Genetics & Heredity
Paschalis Nicolaou, George A. Tanteles, Christina Votsi, Eleni Zamba-Papanicolaou, Savvas S. Papacostas, Kyproula Christodoulou, Yiolanda-Panayiota Christou
Summary: Neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive lysosomal storage disorders characterized by neurodegeneration and cognitive decline. In this study, clinical and genetic findings of three patients from two Greek-Cypriot families with late-infantile juvenile NCL (JNCL) were reported, showing variants in the CLN6 gene and slightly different symptoms. In silico prediction and structural analyses suggest that the identified CLN6 variants are likely pathogenic.
FRONTIERS IN GENETICS
(2021)
Article
Neurosciences
Malabendu Jana, Debashis Dutta, Jit Poddar, Kalipada Pahan
Summary: In this study, gemfibrozil was found to alleviate disease pathology, reduce neuroinflammation, restore the level of TFEB, and decrease the accumulation of SCMAS in an animal model of JNCL. Gemfibrozil treatment also improved locomotor activities. These findings suggest that PPARa activation may be beneficial for JNCL and gemfibrozil may be repurposed for its treatment.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Meagan D. McLaren, Sabateeshan Mathavarajah, William D. Kim, Shyong Q. Yap, Robert J. Huber
Summary: The study reveals the important roles of CLN5 in growth and development processes, with CLN5 deficiency affecting cell proliferation, viability, and autophagic flux. Loss of CLN5 in the early stages of multicellular development impacts cell aggregation and autophagic levels. Post-mound formation, CLN5 deficiency results in developmental abnormalities affecting spore morphology, germination, and viability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Hiroyasu Komiya, Hideyuki Takeuchi, Yuki Ogawa, Yuki Hatooka, Keita Takahashi, Atsuko Katsumoto, Shun Kubota, Haruko Nakamura, Misako Kunii, Mikiko Tada, Hiroshi Doi, Fumiaki Tanaka
Letter
Clinical Neurology
Hiroshi Doi, Masaki Okubo, Ryoko Fukai, Atsushi Fujita, Satomi Mitsuhashi, Keita Takahashi, Misako Kunii, Mikiko Tada, Hiromi Fukuda, Takeshi Mizuguchi, Satoko Miyatake, Noriko Miyake, Jun Sone, Gen Sobue, Hideyuki Takeuchi, Naomichi Matsumoto, Fumiaki Tanaka
ANNALS OF NEUROLOGY
(2020)
Article
Medicine, General & Internal
Cortney E. Heim, Kelsey J. Yamada, Rachel Fallet, Jessica Odvody, Dana M. Schwarz, Elizabeth R. Lyden, Matthew J. Anderson, Roxanne Alter, Debbie Vidlak, Curtis W. Hartman, Beau S. Konigsberg, Chris A. Cornett, Kevin L. Garvin, Naglaa Mohamed, Annaliesa S. Anderson, Tammy Kielian
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Immunology
Matthew Beaver, Dragana Lagundzin, Ishwor Thapa, Junghyae Lee, Hesham Ali, Tammy Kielian, Gwenn L. Skar
Summary: Cutibacterium acnes is a common cause of CSF shunt infection, often underestimated due to difficulties in culturing. New diagnostic methods are needed to detect C. acnes infection. Research in animal models showed inflammatory responses and alterations in CSF proteome during C. acnes infection, suggesting potential diagnostic strategies.
INFECTION AND IMMUNITY
(2021)
Article
Immunology
Amy L. Aldrich, Christopher M. Horn, Cortney E. Heim, Lee E. Korshoj, Tammy Kielian
Summary: The study revealed complex transcriptional heterogeneity of microglia, monocytes, and granulocyte subsets in the brain, scalp, and bone flap of mice with S. aureus craniotomy infection. PMNs played a critical role in S. aureus containment, while MDSCs attenuated PMN antibacterial activity.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Hiroshi Horiuchi, Bijay Parajuli, Hiroyasu Komiya, Yuki Ogawa, Shijie Jin, Keita Takahashi, Yasu-Taka Azuma, Fumiaki Tanaka, Akio Suzumura, Hideyuki Takeuchi
Summary: IL-19 deficiency exacerbates multiple sclerosis by promoting Th17 cell infiltration and increasing expression of antigen presentation and Th17 cell differentiation factors. IL-19 suppresses MS pathogenesis by inhibiting macrophage antigen presentation and Th17 cell expansion. Treatment with IL-19 shows significant therapeutic benefits in experimental autoimmune encephalomyelitis.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Lee E. Korshoj, Tammy Kielian
Summary: The rapidly expanding field of immunometabolism has unveiled a complex association between cellular pro-inflammatory and anti-inflammatory activity, showcasing the metabolic profiles of immune cells in neuroinflammation. The review articles in this Special Issue address the roles of different metabolism types in various neurological conditions and discuss potential therapeutic avenues for the future.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Shun Kubota, Hiroshi Doi, Shigeru Koyano, Kenichi Tanaka, Hiroyasu Komiya, Atsuko Katsumoto, Shingo Ikeda, Shunta Hashiguchi, Haruko Nakamura, Ryoko Fukai, Keita Takahashi, Misako Kunii, Mikiko Tada, Hideyuki Takeuchi, Fumiaki Tanaka
Summary: The study identified small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) as an aggregate-interacting protein in neurodegenerative diseases. SGTA was found to interact with polyQ aggregates and reduce their accumulation, suggesting a potential role as a modifier in the molecular pathological mechanisms of various diseases.
Article
Neurosciences
Hiroyasu Komiya, Hideyuki Takeuchi, Yuki Ogawa, Kosuke Suzuki, Akihiro Ogasawara, Keita Takahashi, Yasu-Taka Azuma, Hiroshi Doi, Fumiaki Tanaka
Summary: Neuroinflammation in ALS is regulated by IL-19, as IL-19-deficient mice showed improved motor function and altered expression of both neurotoxic and neuroprotective factors. Inhibition of IL-19 signaling could potentially alleviate symptoms of ALS.
Article
Multidisciplinary Sciences
Satoko Miyatake, Mitsuhiro Kato, Takuma Kumamoto, Tomonori Hirose, Eriko Koshimizu, Takaaki Matsui, Hideyuki Takeuchi, Hiroshi Doi, Keisuke Hamada, Mitsuko Nakashima, Kazunori Sasaki, Akio Yamashita, Atsushi Takata, Kohei Hamanaka, Mai Satoh, Takabumi Miyama, Yuri Sonoda, Momoko Sasazuki, Hiroyuki Torisu, Toshiro Hara, Yasunari Sakai, Yushi Noguchi, Mazumi Miura, Yoko Nishimura, Kazuyuki Nakamura, Hideyuki Asai, Nodoka Hinokuma, Fuyuki Miya, Tatsuhiko Tsunoda, Masami Togawa, Yukihiro Ikeda, Nobusuke Kimura, Kaoru Amemiya, Asako Horino, Masataka Fukuoka, Hiroko Ikeda, Goni Merhav, Nina Ekhilevitch, Masaki Miura, Takeshi Mizuguchi, Noriko Miyake, Atsushi Suzuki, Shouichi Ohga, Hirotomo Saitsu, Hidehisa Takahashi, Fumiaki Tanaka, Kazuhiro Ogata, Chiaki Ohtaka-Maruyama, Naomichi Matsumoto
Summary: The study identified de novo ATP1A3 variants causing a severe form of polymicrogyria with epilepsy and developmental delay, distinct from traditional clinical features of AHC, RDP, or CAPOS. This suggests a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.
Article
Immunology
Lee E. Korshoj, Wen Shi, Bin Duan, Tammy Kielian
Summary: The blood-brain barrier selectively restricts molecule entry into the central nervous system, creating challenges for treating infections. Nanoparticle systems offer promising solutions by crossing the BBB with specific functionality, increasing cellular targeting, controlled release of therapeutic agents, and enhanced bioavailability. These systems can potentially enhance treatment of CNS disorders by modulating immune cell polarization.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Materials Science, Multidisciplinary
Samuel Ruiz, Fei Wang, Lei Liu, Yongfeng Lu, Bin Duan, Lee E. Korshoj, Tammy Kielian, Bai Cui
Summary: Ag nanoparticles were synthesized using a nanosecond pulsed laser ablation process, and their antibacterial properties were studied, showing potential for biomedical applications.
JOURNAL OF LASER APPLICATIONS
(2022)
Review
Immunology
Zachary Van Roy, Tammy Kielian
Summary: Epigenetics focuses on adaptable transcriptional regulation, influencing cell identity and function. During CNS infection, epigenetic mechanisms play a significant role in controlling immune cell maturation and antimicrobial properties. Researchers use epigenetic marks to organize immune cell populations' activation states and inflammatory processes in response to CNS infection.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Blake P. Bertrand, Cortney E. Heim, Sean C. West, Sujata S. Chaudhari, Hesham Ali, Vinai C. Thomas, Tammy Kielian
Summary: Biofilms formed by Staphylococcus aureus on medical devices are a significant healthcare burden, and a type of white blood cell, G-MDSCs, promote biofilm persistence by inhibiting the activity of other immune cells. This study found that S. aureus promotes biofilm formation and survival through formate metabolism.
INFECTION AND IMMUNITY
(2022)
Article
Immunology
Joseph Menousek, Christopher M. Horn, Cortney E. Heim, Zachary Van Roy, Lee E. Korshoj, Tammy Kielian
Summary: This study compares the phagocytic capacity of microglia and leukocytes in vitro and in vivo using a mouse model of craniotomy infection. The results show that microglial uptake of Staphylococcus aureus is limited in vivo, while other leukocyte populations exhibit phagocytic activity. Single-cell RNA sequencing reveals transcriptional differences between phagocytic and nonphagocytic cells, highlighting the importance of reactive oxygen species, lysosome, iron uptake, and transport pathways in phagocytic cells.
JOURNAL OF IMMUNOLOGY
(2022)