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
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)
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)
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
Jillian M. Cameron, John A. Damiano, Bronwyn Grinton, Patrick W. Carney, Penny McKelvie, Peter Silbert, Nicholas Lawn, Ingrid E. Scheffer, Karen L. Oliver, Michael S. Hildebrand, Samuel F. Berkovic
Summary: This study analyzed the phenotypic features of a group of patients with protracted CLN3 disease in order to improve recognition of the disorder. The results showed that visual impairment was the initial symptom, with onset at 5-9 years, similar to classic CLN3 disease. The disease is often accompanied by progressive generalized and focal seizures.
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
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
Endocrinology & Metabolism
David E. Sleat, Whitney Banach-Petrosky, Katherine E. Larrimore, Yuliya Nemtsova, Jennifer A. Wiseman, Allison Najafi, Dymonn Johnson, Timothy A. Poole, Keigo Takahashi, Jonathan D. Cooper, Peter Lobel
Summary: Late-infantile neuronal ceroid lipofuscinosis (LINCL) and juvenile neuronal ceroid lipofuscinosis (JNCL) are inherited neurodegenerative diseases caused by mutations in the genes encoding lysosomal proteins TPP1 and CLN3, respectively. While enzyme replacement therapy has been successful for LINCL, effective treatments for JNCL are lacking due to unknown CLN3 protein function and limited robust animal models. Through creating a double mutant mouse model, this study found that the phenotype of the double mutant closely resembled that of the single TPP1 mutant, indicating potential use in JNCL therapy development. Additionally, analysis of brain proteomic changes in these models identified potential biomarker candidates for LINCL and altered lysosomal proteins in the Cln3 mutant animals.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
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
Clinical Neurology
Eva Wibbeler, Miriam Nickel, Christoph Schwering, Angela Schulz, Jonathan W. Mink
Summary: This study aimed to determine the validity and reliability of the UBDRS rating scale for CLN3 disease in an independent sample. After evaluating 13 individuals with CLN3 disease, it was concluded that UBDRS has excellent interrater reliability and construct validity.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2022)
Article
Endocrinology & Metabolism
Joanna Karolina Purzycka-Olewiecka, Katarzyna Hetmanczyk-Sawicka, Tomasz Kmiec, Dominika Szczesniak, Joanna Trubicka, Maciej Krawczynski, Maciej Pronicki, Agnieszka Lugowska
Summary: Ceroid lipofuscinosis type 3 (CLN3) is a neurodegenerative metabolic disease characterized by progressive visual loss, epilepsy, and dementia. Lipofuscin deposits and vacuolized lymphocytes are indicative of CLN3 diagnosis. The most common cause of CLN3 is a large deletion of 1.02 kb in exons 7 and 8 of the CLN3 gene. This study reports 4 patients from 2 families who experienced visual deterioration as the initial clinical sign, followed by neurological symptoms. All patients had the 1.02 kb deletion in the CLN3 gene detected. The presence of abnormal structures and the economic feasibility of the 1.02 kb deletion test support its use in diagnosing CLN3.
METABOLIC BRAIN DISEASE
(2023)
Letter
Clinical Neurology
Jan-Niklas Hochstein, A. Schulz, M. Nickel, S. Lezius, M. Grosser, J. Fiehler, J. Sedlacik, U. Lobel
Summary: By analyzing MRI scans and clinical evaluations of patients with CLN3 disease, we found that supratentorial cortical gray matter volume is a sensitive parameter for assessing disease progression and may serve as a reliable outcome measure for evaluating experimental therapies.
Article
Clinical Neurology
Jan-Niklas Hochstein, A. Schulz, M. Nickel, S. Lezius, M. Grosser, J. Fiehler, J. Sedlacik, U. Lobel
Summary: This study analyzed the volumetric development of grey matter, white matter, and lateral ventricles in patients with CLN3 disease, and found that the supratentorial cortical grey matter volume is a sensitive parameter for assessing disease progression and evaluating experimental therapies.
Article
Neurosciences
Song Xue, Feng Kong, Yiying Song, Jia Liu
Summary: This study used resting-state functional magnetic resonance imaging to explore the relationship between individual's spontaneous neural activity and social interaction anxiety in a nonclinical population. The results showed that social interaction anxiety was correlated with the fractional amplitude of low-frequency fluctuations in several brain regions, and that emotional intelligence partially mediated this relationship. This study provides evidence for the neural basis of social interaction anxiety in the normal population and highlights the role of emotional intelligence in this anxiety.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Katsuyuki Yamaguchi, Takuya Yazawa
Summary: This study provides morphometric data on the development of the human medullary arcuate nucleus (AN) by examining the brains of preterm and perinatal infants. The results show that AN morphology demonstrates asymmetry and individual variability during the fetal period. The volume and neuronal number of AN increase exponentially with age, while neuronal density decreases exponentially. The AN may undergo neuron death and neuroblasts production after mid-gestation.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Zhan Zhou, Weixin Dai, Tianxiao Liu, Min Shi, Yi Wei, Lifei Chen, Yubo Xie
Summary: Studies have shown that propofol-induced neurotoxicity is caused by disruption of mitochondrial fission and fusion, leading to an energy supply imbalance for developing neurons. Healthy mitochondria released by astrocytes can migrate to compromised neurons to mitigate propofol-induced neurotoxicity, but the exact mechanisms involved still need further clarification.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
An Chen, Song Hao, Yongpeng Han, Yang Fang, Yibei Miao
Summary: This study explores the efficacy of two forms of BCI attention training games and finds that physical games may be more effective than video games. The research also offers valuable insights for future game design from a neuroscience perspective.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Lina Liu, Luran Liu, Yunting Lu, Tianyuan Zhang, Wenting Zhao
Summary: This study reveals that GDI1 serves as a potential diagnostic biomarker for AD and inhibition of GDI1 can attenuate Aβ-induced neurotoxicity. The findings offer new insights for the treatment of AD.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Zahra Gholami, Ava Soltani Hekmat, Ali Abbasi, Kazem Javanmardi
Summary: This study investigated the effects of alamandine on allodynia in a rat model and found the presence of MrgD receptors in the vlPAG and RVM regions. Microinjection of alamandine resulted in a significant increase in paw withdrawal threshold and could be blocked by an MrgD receptor antagonist. Upregulation of MrgD receptor expression following allodynia induction suggests a potential compensatory mechanism in response to pain.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Mingliang Xu, Lei Xia, Junjie Li, Yehong Du, Zhifang Dong
Summary: This study found that DHF effectively alleviates sevoflurane-induced cognitive impairment in developing mice by restoring the balance between tau O-GlcNAcylation and phosphorylation. Therefore, DHF has the potential to be a therapeutic agent for treating cognitive impairment associated with anesthetics, such as sevoflurane.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Tsubasa Mitsutake, Hisato Nakazono, Takanori Taniguchi, Hisayoshi Yoshizuka, Maiko Sakamoto
Summary: The posterior parietal cortex plays a crucial role in postural stability, and transcranial electrical stimulation of this region can modulate physical control responses. This study found that cathodal stimulation significantly decreased joint angular velocity in multiple directions, while there were no significant differences with transcranial random noise stimulation.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Xishuai Yang, Wei Zhang, Xueli Chang, Zuopeng Li, Runquan Du, Junhong Guo
Summary: This study aims to evaluate the efficacy of low-dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). The results showed that low-dose RTX treatment led to significant improvements in clinical symptoms and quality of life for patients with MuSK-MG.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Jian Zhang, Shunyuan Guo, Rong Tao, Fan Wang, Yihong Xie, Huizi Wang, Lan Ding, Yuejian Shen, Xiaoli Zhou, Junli Feng, Qing Shen
Summary: This study established an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 and found that marine-derived plasmalogens (Pls) could alleviate cognitive impairments of AD zebrafish by reversing athletic impairment and altering the expression levels of genes related to oxidative stress, ferroptosis, synaptic dysfunction, and apoptosis.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Lu Li, Jiaqi Ren, Qi Fang, Liqiang Yu, Jintao Wang
Summary: ICU-AW is a common and severe neuromuscular complication in critically ill patients. Electrophysiological examination is essential for accurate diagnosis and early prediction of the disease. This study aimed to establish and validate an ICU-AW predictive model in SIRS patients, providing a practical tool for early clinical prediction.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Ahmad Alipour, Roghayeh Mohammadi
Summary: The present study aimed to investigate the separate and combined effects of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and left dorsolateral prefrontal cortex (F3) regions on pain relief in patients with type-2 diabetes suffering from neuropathic pain (NP). The results showed that tDCS had the potential to induce pain relief in patients with type-2 diabetes suffering from NP. The mean perceived pain intensity in the posttest was lower in the M1 stimulation group than in the F3 stimulation group. However, more trials with larger sample sizes are necessary to define clinically relevant effects.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Eduardo J. Fusse, Franciele F. Scarante, Maria A. Vicente, Mariana M. Marrubia, Flavia Turcato, Davi S. Scomparin, Melissa A. Ribeiro, Maria J. Figueiredo, Tamires A. V. Brigante, Francisco S. Guimaraes, Alline C. Campos
Summary: Repeated exposure to psychosocial stress alters the endocannabinoid system and affects brain regions associated with emotional distress. Enhancing the effects of endocannabinoids through pharmacological inhibition induces an anti-stress behavioral effect, possibly mediated by the mTOR signaling pathway.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Giulia Agostoni, Luca Bischetti, Federica Repaci, Margherita Bechi, Marco Spangaro, Irene Ceccato, Elena Cavallini, Luca Fiorentino, Francesca Martini, Jacopo Sapienza, Mariachiara Buonocore, Michele Francesco D'Incalci, Federica Cocchi, Carmelo Guglielmino, Roberto Cavallaro, Marta Bosia, Valentina Bambini
Summary: This study found a general impairment in humor comprehension in individuals with schizophrenia, with mental jokes being more difficult for both patients and controls. Humor comprehension was closely associated with the patients' overall pragmatic and linguistic profile, while the association with Theory of Mind (ToM) was minimal. Another notable finding was the increased appreciation of humor in individuals with schizophrenia, who rated jokes as funnier than controls did, regardless of whether they were correctly or incorrectly completed. The funniness ratings were not predicted by any measure, suggesting a dimension of humor untied to cognition or psychopathology.
NEUROSCIENCE LETTERS
(2024)
Article
Neurosciences
Xiuping Gong, Qi Li, Yang Liu
Summary: This study demonstrates that Sev targets CREBBP to inhibit ALG13 transcription, leading to hippocampal damage and cognitive impairment.
NEUROSCIENCE LETTERS
(2024)