Article
Genetics & Heredity
Szilvia E. Mezey, Josef P. Kapfhammer, Etsuko Shimobayashi
Summary: This study investigates the pathogenesis of SCA14 using a mouse model. The findings suggest that SCA14-associated gene modifications primarily involve cerebellar development rather than changes in mature animals.
Article
Neurosciences
Etsuko Shimobayashi, Josef P. Kapfhammer
Summary: SCA14 is a disease caused by mutations in PKC gamma, but it is unclear whether increased or decreased PKC gamma activity is involved in the pathogenesis of SCA14. A new mouse model related to SCA14 with increased PKC activity in Purkinje cells was presented in the study, showing an ataxia phenotype and Purkinje cell dysfunction. This model may provide valuable insights into the pathogenesis of SCA.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Neurosciences
Josef P. Kapfhammer, Etsuko Shimobayashi
Summary: Spinocerebellar ataxias (SCAs) are hereditary neurodegenerative diseases characterized by mutations affecting cerebellar Purkinje cells. One subtype, SCA14, is caused by mutations in the Protein Kinase C gamma (PKCγ) gene, which leads to increased basal activity of PKCγ. This increased activity may be the cause of most forms of SCA14 and could be involved in the pathogenesis of related subtypes. Additionally, the pathogenesis of SCAs may be driven by dysfunction of Purkinje cells rather than cell death and loss.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Tomoko Ohta, Yuri Morikawa, Masahiro Sato, Ayumu Konno, Hirokazu Hirai, Yuki Kurauchi, Akinori Hisatsune, Hiroshi Katsuki, Takahiro Seki
Summary: The study showed that D-cysteine can improve impaired dendritic development in PCs caused by SCA-causing proteins, suggesting therapeutic potential for both in vitro and in vivo SCA models.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Polina A. Egorova, Ksenia S. Marinina, Ilya B. Bezprozvanny
Summary: Distorted neuronal calcium signaling is observed in various neurodegenerative disorders, including spinocerebellar ataxias (SCAs). In SCA2, cerebellar Purkinje cells (PCs) are primarily affected and show disturbances in calcium homeostasis. Recent studies have highlighted the role of STIM1 in regulating neuronal calcium signaling in cerebellar PCs. siRNA targeting STIM1 expression in cerebellar PCs alleviates calcium signaling disruption, restores spine loss, and improves motor decline in SCA2-58Q mice, indicating the potential therapeutic target of the STIM1-mediated signaling pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Review
Cell Biology
Caila A. Pilo, Alexandra C. Newton
Summary: Protein kinase C gamma (PKCγ) isozyme plays a role in signal transduction within cells and its aberrant expression may be associated with certain cancers and neurodegenerative disorders such as SCA14. However, the exact mechanisms and roles of PKCγ in these diseases are still not fully understood.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Neurosciences
Polina A. Egorova, Ilya B. Bezprozvanny
Summary: Spinocerebellar ataxia type 2 (SCA2) is an incurable hereditary disorder characterized by cerebellar degeneration and ataxic symptoms. Mutations in the ATXN2 gene lead to impaired RNA metabolism and loss of function of the ataxin-2 protein, while also enhancing calcium signaling. Abnormal activity of cerebellar Purkinje cells (PCs) is associated with various ataxic disorders. Activation of SK channels has shown promising results in improving motor function and PC morphology in SCA2 mice, suggesting it as a potential therapeutic approach for SCA2 and other diseases with cerebellar degeneration.
Review
Biochemistry & Molecular Biology
Qin-Wei Wu, Josef P. Kapfhammer
Summary: This article summarizes the clinical features of spinocerebellar ataxias (SCAs) and the role of gene function in cerebellar Purkinje cell development. It also discusses the relationship between SCA pathogenesis and neurodevelopment, with a focus on the potential common pathway involved in these diseases, namely the mGluR1-PKC gamma signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Harvey Perez, May F. Abdallah, Jose Chavira, Angelina S. Norris, Martin T. Egeland, Karen L. Vo, Callan L. Buechsenschuetz, Valentina Sanghez, Jeannie L. Kim, Molly Pind, Kotoka Nakamura, Geoffrey G. Hicks, Richard A. Gatti, Joaquin Madrenas, Michelina Iacovino, Peter J. McKinnon, Paul J. Mathews
Summary: By introducing null mutations in both the Atm and Aptx genes in mice, researchers have created a novel mouse model that exhibits progressively severe ataxic phenotype and cerebellar molecular layer atrophy. The perturbations significantly alter the biophysical properties of cerebellar Purkinje neurons and their neural activity, correlating with cerebellar atrophy and ataxia over the animal's first year of life. Additionally, the double mutant mice also show a predisposition to cancer and immune abnormalities, resembling symptoms of A-T.
Article
Neurosciences
Ksenia S. Marinina, Ilya B. Bezprozvanny, Polina A. Egorova
Summary: Spinocerebellar ataxia type 2 (SCA2) is a hereditary disorder caused by an expansion of polyglutamine in the ataxin-2 protein. Although primarily affecting the cerebellum, recent evidence suggests that SCA2 also impacts cognitive abilities and emotional processing. Through the use of transgenic SCA2-58Q mice, researchers found that the mutant ataxin-2 protein expressed in cerebellar Purkinje cells led to anxiolytic behavior, decline in spatial memory, and depressive-like state. These findings support the involvement of the cerebellum in cognitive control and emotional regulation.
Article
Cell Biology
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Andrey N. Shuvaev, Yana Fritsler, Elena D. Khilazheva, Angelina Mosyagina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by mutant ATXN1 protein accumulation, leading to deficits in motor performance and synaptic plasticity. The disease affects both neurons and glial cells.
Review
Clinical Neurology
Marija Cvetanovic, Michelle Gray
Summary: Neurodegenerative diseases are characterized by specific neuronal cell type degeneration in certain brain regions, leading to varied clinical presentations. Dysfunction in non-neuronal glial cell types also contributes to the pathogenesis of these diseases. Understanding the role and regulation of glial cells in disease may lead to the development of new neurotherapeutic approaches.
Article
Biochemistry & Molecular Biology
Victor Olmos, Evrett N. Thompson, Neha Gogia, Kimberly Luttik, Vaishnavi Veeranki, Luhan Ni, Serena Sim, Kelly Chen, Diane S. Krause, Janghoo Lim
Summary: This study reveals that mutant ATAXIN-1 can lead to diverse splicing events and contribute to the pathogenesis of spinocerebellar ataxia type 1. The researchers identify Rbfox1 as a mediator of mutant ATAXIN-1's effect on misregulated alternative splicing and demonstrate that manipulation of Rbfox1 expression can modify neurodegenerative phenotypes in a Drosophila model. These findings provide valuable insights into the molecular mechanisms and potential therapeutic strategies for spinocerebellar ataxia type 1.
HUMAN MOLECULAR GENETICS
(2023)
Review
Clinical Neurology
Marija Cvetanovic, Michelle Gray
Summary: Neurodegenerative diseases are characterized by the degeneration of specific neuronal cell types in the brain, leading to various clinical presentations. In diseases like Huntington's disease (HD) and spinocerebellar ataxias (SCA), the degeneration of specific neurons, such as striatal medium spiny neurons (MSNs) in HD or cerebellar Purkinje cells in SCA, contributes to the observed abnormalities in motor function. While research has primarily focused on understanding dysregulated mechanisms in these neuronal cell types, recent studies suggest that dysfunction in non-neuronal glial cell types also contributes to disease pathogenesis. This article explores the role of glial cells in HD and SCA and the potential for developing glia-focused neurotherapeutics.
Article
Biochemistry & Molecular Biology
Martina Sucha, Simona Benediktova, Filip Tichanek, Jan Jedlicka, Stepan Kapl, Dana Jelinkova, Zdenka Purkartova, Jan Tuma, Jitka Kuncova, Jan Cendelin
Summary: This study aimed to explore the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. However, the results showed that edaravone did not have any plausible therapeutic effect on either behavioral dysfunctions or other disease hallmarks in SCA1 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Etsuko Shimobayashi, Wolfgang Wagner, Josef P. Kapfhammer
MOLECULAR NEUROBIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Xinzhou Zhu, Andrea Zelmer, Josef P. Kapfhammer, Sven Wellmann
Article
Neurosciences
S. Sinoy, S. M. Fayaz, K. D. Charles, V. K. Suvanish, Josef P. Kapfhammer, G. K. Rajanikant
MOLECULAR NEUROBIOLOGY
(2017)
Article
Neurosciences
Etsuko Shimobayashi, Josef P. Kapfhammer
Review
Neurosciences
Etsuko Shimobayashi, Josef P. Kapfhammer
CURRENT NEUROPHARMACOLOGY
(2018)
Article
Neurosciences
Jakub Trzesniewski, Sandrine Altmann, Levy Jager, Josef P. Kapfhammer
EXPERIMENTAL NEUROLOGY
(2019)
Article
Neurosciences
Sabine C. Winkler, Etsuko Shimobayashi, Josef P. Kapfhammer
MOLECULAR NEUROBIOLOGY
(2020)
Article
Neurosciences
Etsuko Shimobayashi, Josef P. Kapfhammer
Summary: SCA14 is a disease caused by mutations in PKC gamma, but it is unclear whether increased or decreased PKC gamma activity is involved in the pathogenesis of SCA14. A new mouse model related to SCA14 with increased PKC activity in Purkinje cells was presented in the study, showing an ataxia phenotype and Purkinje cell dysfunction. This model may provide valuable insights into the pathogenesis of SCA.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Qin-Wei Wu, Josef P. Kapfhammer
Summary: STK17B is strongly expressed in cerebellar Purkinje cells and is regulated by PKC phosphorylation. It acts as a downstream effector of PKC, influencing the morphological changes of Purkinje cells and possibly playing a role in the pathology of SCAs.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Szilvia E. Mezey, Josef P. Kapfhammer, Etsuko Shimobayashi
Summary: This study investigates the pathogenesis of SCA14 using a mouse model. The findings suggest that SCA14-associated gene modifications primarily involve cerebellar development rather than changes in mature animals.
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)