Article
Cell Biology
Naomi Hartopp, Dawn H. W. Lau, Sandra M. Martin-Guerrero, Andrea Markovinovic, Gabor M. Morotz, Jenny Greig, Elizabeth B. Glennon, Claire Troakes, Patricia Gomez-Suaga, Wendy Noble, Christopher C. J. Miller
Summary: This study investigates the alterations in VAPB-PTPIP51 tethers in the spinal cords of ALS patients and healthy individuals. The findings show a reduction in VAPB protein levels and disrupted VAPB-PTPIP51 tethers in ALS patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yeun Ju Kim, Nivedita Sengupta, Mira Sohn, Amrita Mandal, Joshua G. Pemberton, Uimook Choi, Tamas Balla
Summary: This study reveals that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl-CoA used, leading to preferential routing of the arachidonoyl-enriched species towards PI synthesis. Additionally, the unsaturated forms of PI(4,5P)(2) are replenished faster than the saturated forms during PLC activation, indicating a favored recycling of the unsaturated forms of the PLC-generated hydrolytic products. CDS2 contributes to increased PI resynthesis during PLC activation, while Nir2 contributes to rapid PPIn resynthesis, but the faster re-synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side-chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates and the maintenance of the unique fatty acid profile of PPIn lipids.
Article
Cell Biology
Patricia Gomez-Suaga, Gabor M. Morotz, Andrea Markovinovic, Sandra M. Martin-Guerrero, Elisavet Preza, Natalia Arias, Keith Mayl, Afra Aabdien, Vesela Gesheva, Agnes Nishimura, Ambra Annibali, Younbok Lee, Jacqueline C. Mitchell, Selina Wray, Christopher Shaw, Wendy Noble, Christopher C. J. Miller
Summary: This study reveals that hexanucieotide repeat expansions in C9orf72 disrupt the ER-mitochondria signalling and VAPB-PTPIP51 tethers, leading to neurotoxicity. The interaction between VAPB-PTPIP51 is disrupted by neurotoxic DPRs, potentially involving the activation of GSK3β. Furthermore, these DPRs also disrupt the delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB-PTPIP51 tethers. These findings identify a new molecular target for mutant C9orf72-mediated toxicity.
Review
Cell Biology
Junsheng Chen, Arthur Bassot, Fabrizio Giuliani, Thomas Simmen
Summary: ALS is a devastating neurodegenerative disease without cure, with a potential involvement of dysfunctional mitochondria-endoplasmic reticulum contacts (MERCs) leading to altered mitochondrial bioenergetics and oxidative stress. VAPB and VCP are key players in ALS pathogenesis, interacting with other mutant proteins and causing ER stress, inflammation, and motor neuron death. The dysfunction of MERCs in ALS triggers a cascade of pathological changes in the cell.
Article
Clinical Neurology
Dallah Yoo, Wonjae Lee, Seung-Jae Lee, Jung-Joon Sung, Gye Sun Jeon, Jae-Jun Ban, Chaewon Shin, Jungho Kim, Hyo Sun Kim, Tae-Beom Ahn
Summary: In this study, a Korean family with Parkinson's disease or amyotrophic lateral sclerosis caused by a novel variant of TFG was described. Clinical and in vitro studies supported the pathogenic role of the TFG mutation in alpha-synucleinopathy and TDP-43 proteinopathy, expanding the phenotypic spectrum of TFG and suggesting a pivotal role of endoplasmic reticulum dysfunction during neurodegeneration.
MOVEMENT DISORDERS
(2022)
Review
Cell Biology
Sandra M. Martin-Guerrero, Andrea Markovinovic, Gabor M. Morotz, Shaakir Salam, Wendy Noble, Christopher C. J. Miller
Summary: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two major neurodegenerative diseases and are now known to be associated with each other. Currently, there are no cures or effective treatments for FTD or ALS, necessitating the identification of new therapeutic targets. Recent studies have shown that the damaged signaling between the endoplasmic reticulum (ER) and mitochondria plays a role in FTD/ALS. Restoring this disrupted signaling may have the potential to correct other damaged features of FTD/ALS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
AnnaMari L. Stump, Daniel J. Rioux, Richard Albright, Guiliano L. Melki, Derek C. Prosser
Summary: Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease caused by the loss of motor neurons. A mutation in the VAPB gene, known as the P56S mutation, is linked to familial ALS type 8. This study describes a yeast model for ALS8 using SCS2 and SCS22 genes, which are homologs of VAPB in budding yeast. The model displays similar phenotypes to mammalian cells expressing VAPB(P56S), making it a potential tool for studying the molecular basis of ALS8.
Article
Biochemistry & Molecular Biology
Alexis Martinez, Cristian M. Lamaizon, Cristian Valls, Fabien Llambi, Nancy Leal, Patrick Fitzgerald, Cliff Guy, Marcin M. Kaminski, Nibaldo C. Inestrosa, Brigitte van Zundert, Gonzalo I. Cancino, Andres E. Dulcey, Silvana Zanlungo, Juan J. Marugan, Claudio Hetz, Douglas R. Green, Alejandra R. Alvarez
Summary: Endoplasmic reticulum stress activates c-Abl tyrosine kinase, which translocates to mitochondria. Activated c-Abl interacts with mitochondrial fusion protein MFN2, leading to mitochondrial fragmentation and apoptosis.
Review
Geriatrics & Gerontology
Yu-Mi Jeon, Younghwi Kwon, Shinrye Lee, Hyung-Jun Kim
Summary: The endoplasmic reticulum (ER) is involved in protein quality control and cellular homeostasis. ER stress response pathway, such as unfolded protein response (UPR), occurs when the organelle becomes dysfunctional and misfolded proteins accumulate. This pathway is implicated in neurodegenerative diseases and ALS.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Tim G. Ashlin, Nicholas J. Blunsom, Shamshad Cockcroft
Summary: The article discusses the role of phosphatidylinositol transfer proteins (PITPs) in mobilising PI from the ER to provide substrate for resident kinases for phosphorylation. Recent studies have identified specific and overlapping functions for the three soluble PITPs (PITP alpha, PITP beta and PITPNC1) in phospholipase C signalling, neuronal function, membrane trafficking, viral replication, and cancer metastases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Luyang Xiong, Michael McCoy, Hitoshi Komuro, Xiaoxia Z. West, Valentin Yakubenko, Detao Gao, Tejasvi Dudiki, Amanda Milo, Jacqueline Chen, Eugene A. Podrez, Bruce Trapp, Tatiana Byzova
Summary: ALS is a progressive neurodegenerative disease with no cure, where inflammation and oxidative stress may play a significant role, particularly in patients with the SOD1 mutation. The accumulation of CEP, a DHA peroxidation product, in ALS brains may be linked to activated inflammatory cells and reduced antioxidant activity due to the mutation, highlighting its potential as a hallmark of oxidative damage in neurodegenerative diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Neurosciences
Tyler L. Wells, Jacob R. Myles, Turgay Akay
Summary: ALS is a neurodegenerative disease resulting in progressive motor neuron death and typically fatal within 5 years of diagnosis. Research indicates that silencing C-boutons in ALS mouse models can improve muscle innervation and behavioral capabilities, suggesting that manipulating these synapses in combination with targeted training programs could be beneficial for ALS patients, leading to improved mobility and quality of life.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Yahui Zhu, Yunyun Huo, Jiongming Bai, Mao Li, Hongfen Wang, Jiao Wang, Xusheng Huang
Summary: This study aimed to investigate the relationship between serum Cystatin C (CysC) and survival in ALS patients. The results showed that ALS patients with high CysC levels had shorter median survival than those with lower CysC levels, and serum CysC level might be an independent predictor of ALS survival.
NEUROLOGICAL SCIENCES
(2023)
Article
Immunology
Run Fang, Qifei Jiang, Xinying Jia, Zhengfan Jiang
Summary: The cGAS-STING pathway is involved in cytoplasmic DNA-induced innate immune response. STING is activated through translocation from the endoplasmic reticulum and polymerization at the Golgi triggered by cyclic-GMP-AMP (cGAMP) and sulfated glycosaminoglycans, respectively. This study reveals that Armadillo-like helical domain-containing protein 3 (ARMH3) is critical for STING activation and acts as a bridge between STING and phosphatidylinositol 4-kinase beta (PI4KB) to generate PI4P, which directs STING trafficking from the Golgi to endosomes through PI4P-binding proteins AP-1 and GGA2.
Review
Behavioral Sciences
Sanjeev Kharel, Rajeev Ojha, Veeramani Preethish-Kumar, Riwaj Bhagat
Summary: This study investigated the role of C-reactive protein (CRP) in amyotrophic lateral sclerosis (ALS). The results showed a significant increase in CRP levels among ALS patients compared to healthy controls in most of the studies. In addition, CRP levels were found to be correlated with ALS functional rating scale and disease progression. However, more large-scale studies are needed to evaluate the value and accuracy of CRP as a prognostic biomarker in ALS, taking into account confounding factors.
BRAIN AND BEHAVIOR
(2022)
Article
Multidisciplinary Sciences
Mira Sohn, Pavlina Ivanova, H. Alex Brown, Daniel J. Toth, Peter Varnai, Yeun Ju Kim, Tamas Balla
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Biochemistry & Molecular Biology
Gergo Gulyas, Gloria Radvanszki, Rita Matuska, Andras Balla, Laszlo Hunyady, Tamas Balla, Peter Varnai
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Cell Biology
Marek K. Korzeniowski, Eva Wisniewski, Barbara Baird, David A. Holowka, Tamas Balla
JOURNAL OF CELL SCIENCE
(2017)
Article
Cell Biology
Roni Levin, Gerald R. V. Hammond, Tamas Balla, Pietro De Camilli, Gregory D. Fairn, Sergio Grinstein
MOLECULAR BIOLOGY OF THE CELL
(2017)
Article
Neurosciences
Tamas Balla
JOURNAL OF PHYSIOLOGY-LONDON
(2018)
Article
Multidisciplinary Sciences
Martin Klima, Daniel J. Toth, Rozalie Hexnerova, Adriana Baumlova, Dominika Chalupska, Jan Tykvart, Lenka Rezabkova, Nivedita Sengupta, Petr Man, Anna Dubankova, Jana Humpolickova, Radim Nencka, Vaclav Veverka, Tamas Balla, Evzen Boura
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Takashi Baba, Daniel J. Toth, Nivedita Sengupta, Yeun Ju Kim, Tamas Balla
Correction
Biochemistry & Molecular Biology
Takashi Baba, Daniel J. Toth, Nivedita Sengupta, Yeun Ju Kim, Tamas Balla
Article
Cell Biology
Joshua G. Pemberton, Yeun Ju Kim, Nivedita Sengupta, Andrea Eisenreichov, Daniel J. Toth, Evzen Boura, Tamas Balla, Jana Humpoiickova
JOURNAL OF CELL BIOLOGY
(2020)
Article
Cell Biology
Alfredo Sanchez-Solano, Nancy Corral, Guadalupe Segura-Covarrubias, Maria Luisa Guzman-Hernandez, Ivan Arechiga-Figueroa, Silvia Cruz-Rangel, Patricia Perez-Cornejo, Jorge Arreola
Article
Education, Scientific Disciplines
Patricia Perez-Cornejo, Nancy E. Corral-Fernandez, Maria Luisa Guzman-Hernandez, Chaya Gopalan
Summary: Medical students learned about the relationship between nutrition, obesity, and diabetes through laboratory exercises and blood glucose response tests, with teaching intervention showing positive outcomes.
ADVANCES IN PHYSIOLOGY EDUCATION
(2021)
Article
Physiology
Victor De la Rosa, Maria Luisa Guzman-Hernandez, Elisa Carrillo
Summary: KCNQ channels play a crucial role in the physiology of various cell types, particularly in neurons of the central nervous system. Activating these channels helps control neuronal activity and prevent excessive firing. In this study, it was found that triclosan, a widely used bactericide in personal care products, activates KCNQ3 channels, offering new possibilities for the treatment of epilepsy and other hyperexcitability conditions.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yeun Ju Kim, Nivedita Sengupta, Mira Sohn, Amrita Mandal, Joshua G. Pemberton, Uimook Choi, Tamas Balla
Summary: This study reveals that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl-CoA used, leading to preferential routing of the arachidonoyl-enriched species towards PI synthesis. Additionally, the unsaturated forms of PI(4,5P)(2) are replenished faster than the saturated forms during PLC activation, indicating a favored recycling of the unsaturated forms of the PLC-generated hydrolytic products. CDS2 contributes to increased PI resynthesis during PLC activation, while Nir2 contributes to rapid PPIn resynthesis, but the faster re-synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side-chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates and the maintenance of the unique fatty acid profile of PPIn lipids.
Article
Endocrinology & Metabolism
Stephanie Constantin, Srdjan J. Sokanovic, Yuta Mochimaru, Kosara Smiljanic, Sonja Sivcev, Rafael M. Previde, Susan Wray, Tamas Balla, Stanko S. Stojilkovic
Summary: PI4-kinase A plays a key role in the postnatal development and maintenance of a functional gonadotroph population in mouse reproduction. Knocking out this enzyme leads to infertility, underdeveloped gonads and reproductive tracts, and lack of puberty. These findings have important implications for understanding the mechanisms of postnatal reproductive development.
Review
Cell Biology
Peter Varnai, Gergo Gulyas, Daniel J. Toth, Mira Sohn, Nivedita Sengupta, Tamas Balla