Review
Neurosciences
Neha Mohan, Liang Qiang, Gerardo Morfini, Peter W. Baas
Summary: Mutations in the SPAST gene cause Hereditary Spastic Paraplegia by compromising the function of spastin and giving it toxic gain-of-function properties. Therapeutic strategies are discussed to alleviate symptoms in patients with SPAST-based Hereditary Spastic Paraplegia, also known as SPG4-HSP.
Article
Clinical Neurology
Rui Chen, Shiyue Du, Yanyi Yao, Lu Zhang, Junyu Luo, Yinhua Shen, Zhenping Xu, Xiaomei Zeng, Luoying Zhang, Mugen Liu, Chuang Yin, Beisha Tang, Jun Tan, Xuan Xu, Jing Yu Liu
Summary: Genetic testing in three large Chinese families revealed a novel variant in the SPAST gene, resulting in two truncated proteins with different effects on microtubules. This study suggests that mutations in SPAST leading to premature stop codons may exert their pathogenic effects through isoform-specific toxic effects rather than haploinsufficiency.
MOVEMENT DISORDERS
(2022)
Article
Oncology
Xing-Chen Wang, Rui-Han Liu, Ting Wang, Yanling Wang, Yan Jiang, Dan-Dan Chen, Xin-Yu Wang, Tong-Shu Hou, Qing-Xia Kong
Summary: This study reports a mutation causing SPG4 and describes the clinical characteristics of affected family members. All affected individuals in the family exhibited lower limb spasticity and weakness, and only males were affected. Whole-exome sequencing revealed a novel c.1785C>A (p. Ser595Arg) missense mutation in the SPAST gene in all affected individuals. Bioinformatics analysis showed changes in the secondary and tertiary structures of the mutated protein. This novel missense mutation in SPAST supports the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations causing SPG4.
MOLECULAR MEDICINE REPORTS
(2023)
Article
Genetics & Heredity
Jie Wang, Yihan Wu, Hong Dong, Yunpeng Ji, Lichun Zhang, Yaxian Liu, Yueshi Liu, Xin Gao, Yueqi Jia, Xiaohua Wang
Summary: This study identified a disease-causing variant of SPG4 in a Chinese family and found that SPAST mutations may not always act through haploinsufficiency. The intracellular accumulation of truncated spastin could be a potential pathological mechanism of SPG4.
BMC MEDICAL GENOMICS
(2023)
Review
Medicine, Research & Experimental
Qiuling Liu, Guowei Zhang, Zhisheng Ji, Hongsheng Lin
Summary: Spastin is a microtubule-severing enzyme identified from mutations of hereditary spastic paraplegia, and recent studies have uncovered its mechanistic processes in microtubule-severing activity as well as its impact on novel molecular mechanisms in cellular biological pathways.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Clinical Neurology
Seyyed-Saleh Hashemi, Reza Hajati, Atefeh Davarzani, Mohammad Rohani, Fardad DanaeeFard, Mohammad Masoud Rahimi Bidgoli, Farzad Fatehi, Ariana Kariminejad, Hossein Najmabadi, Shahriar Nafissi, Afagh Alavi
Summary: Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder with different inheritance patterns, and most autosomal-dominant HSPs (AD-HSPs) are associated with mutations in the SPAST gene. Anticipation may be a common finding in SPG4 families, with affected individuals showing earlier age-at-onset in successive generations. This study suggests that SPAST is a key gene in families with pure forms of AD-HSP and anticipation, indicating a strong genotype-phenotype correlation.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Evren Onay Ucar, Aslihan Sengelen, Elif Mertoglu Kamali
Summary: The study reveals that heat shock response (HSR) is closely related to therapeutic resistance of gliomas. Resveratrol (RSV) shows potential as an experimental agent for glioblastoma (GB) therapy, but the role of heat shock proteins (Hsps) in RSV efficacy remains unclear. The findings suggest that silencing Hsp27, Hsp60, Hsp70, and Hsp90 makes glioma cells more sensitive to RSV treatment, making these Hsps potential therapeutic targets for GB treatment.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Pang-Yen Liu, Hsin-Hsueh Shen, Ching-Wen Kung, Shu-Ying Chen, Chia-Hsien Lu, Yen-Mei Lee
Summary: Sepsis is a life-threatening organ dysfunction syndrome caused by bacterial infections, characterized by systemic inflammatory responses and elevated oxidative stress leading to multiple organ dysfunction and disseminated intravascular coagulation. Heat shock protein 70 (HSP70) plays a protective role in cellular homeostasis, while HSP 90 inhibitors have been reported to have anti-inflammatory effects through the induction of HSP70.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Christian Tibor Josef Magyar, Yogesh K. Vashist, Deborah Stroka, Corina Kim-Fuchs, Martin D. Berger, Vanessa M. Banz
Summary: HSP90 inhibitors may have potential efficacy in the treatment of gastrointestinal cancers, but more research is needed to determine which patient subgroups and at what time point these inhibitors may be beneficial.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Benan Temizci, Seren Kucukvardar, Arzu Karabay
Summary: The microtubule-severing protein Spastin co-localizes with actin in migratory glioblastoma cells and is involved in their migration and invasion capacity. It has been discovered that Spastin interacts with the cis-trans isomerase Pin1 through binding to phosphorylated Pin1 recognition motifs in the microtubule-binding domain. This interaction guides Spastin towards actin filaments and contributes to the increased migration and invasion abilities of glioblastoma cells.
Article
Cell Biology
Stojan Peric, Vladana Markovic, Ayse Candayan, Els De Vriendt, Nikola Momcilovic, Andrija Savic, Natasa Dragasevic-Miskovic, Marina Svetel, Zorica Stevic, Ivo Bozovic, Sarlota Mesaros, Jelena Drulovic, Ivana Basta, Igor Petrovic, Olivera Tamas, Milija Mijajlovic, Ivana Novakovic, Dragoslav Sokic, Albena Jordanova
Summary: The study analyzed the genetic causes of HSP in adult Serbian patients and found a high genetic diversity in this population. The findings have important implications for molecular diagnostics and broaden the knowledge on the genetic epidemiology of HSP.
Article
Genetics & Heredity
Keisuke Shimozono, Haitian Nan, Takanori Hata, Kozo Saito, Yeon-Jeong Kim, Hiroaki Nagatomo, Toshihisa Ohtsuka, Schuichi Koizumi, Yoshihisa Takiyama
Summary: This study generated a mouse model of SPG80 that reproduces the phenotype of patients with the disease. By observing the pathological changes in the mice, the role of the UBAP1 gene mutation in the development of the disease and its impact on vesicular trafficking were revealed. This model provides an important tool for further studying the molecular pathogenesis of SPG80 and screening therapeutic agents.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Multidisciplinary Sciences
A. King Cada, Mark R. Pavlin, Juan P. Castillo, Alexander B. Tong, Kevin P. Larsen, Xuefeng Ren, Adam L. Yokom, Feng-Ching Tsai, Jamie Shiah, Patricia M. Bassereau, Carlos J. Bustamante, James H. Hurley
Summary: The endosomal sorting complexes required for transport (ESCRT) system is a membrane scission machinery that catalyzes the budding and scission of membranes. In this study, researchers investigated the capability of CHMP1B and IST1, two ESCRT-III subunits, to sever membranes on their own or in concert with VPS4 or spastin. They found that CHMP1B and IST1 can form stable scaffolds on membrane nanotubes but do not lead to scission. However, when an additional extensional force was applied, the CHMP1B-IST1 scaffolded tubes were severed, suggesting a friction-driven scission mechanism. The protein spastin was found to colocalize with CHMP1B-enriched sites but did not disassemble the CHMP1B-IST1 coat from the membrane. VPS4, on the other hand, resolubilized CHMP1B and IST1 without leading to scission. These results demonstrate that CHMP1B-IST1 can sever membranes by a friction-driven mechanism independent of VPS4 and spastin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Gautam Wali, Sue-Faye Siow, Erandhi Liyanage, Kishore R. R. Kumar, Alan Mackay-Sim, Carolyn M. M. Sue
Summary: HSP-SPAST is the most common form of hereditary spastic paraplegia (HSP), causing lower limb spasticity. Both patient-derived cortical neurons and peripheral blood mononuclear cells (PBMCs) show reduced levels of acetylated alpha-tubulin, which can be restored by noscapine treatment. Noscapine treatment can potentially benefit HSP-SPAST patients by increasing acetylated alpha-tubulin levels.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Grace Y. Liu, Shiau-Chi Chen, Gang-Hui Lee, Kritika Shaiv, Pin-Yu Chen, Hsuan Cheng, Shi-Rong Hong, Wen-Ting Yang, Shih-Han Huang, Ya-Chu Chang, Hsien-Chu Wang, Ching-Lin Kao, Pin-Chiao Sun, Ming-Hong Chao, Yian-Ying Lee, Ming-Jer Tang, Yu-Chun Lin
Summary: Microtubules, a crucial cellular structure, have been studied using chemo and optogenetics methods to disassemble specific types of microtubules. The results provide insights into their roles in cellular trafficking, organelle reorganization, and cell stiffness.
Article
Multidisciplinary Sciences
Michael Feichtinger, Tina Stopp, Christian Goebl, Elisabeth Feichtinger, Enrico Vaccari, Ulrike Maedel, Franco Laccone, Monika Stroh-Weigert, Markus Hengstschlaeger, Wilfried Feichtinger, Juergen Neesen
Correction
Multidisciplinary Sciences
Michael Feichtinger, Tina Stopp, Christian Goebl, Elisabeth Feichtinger, Enrico Vaccari, Ulrike Maedel, Franco Laccone, Monika Stroh-Weigert, Markus Hengstschlaeger, Wilfried Feichtinger, Juergen Neesen
Article
Biochemistry & Molecular Biology
Aleksandra E. Kornienko, Irena Vlatkovic, Juergen Neesen, Denise P. Barlow, Florian M. Pauler
Review
Toxicology
Claudia Gundacker, Juergen Neesen, Elisabeth Straka, Isabella Ellinger, Helmut Dolznig, Markus Hengstschlaeger
ARCHIVES OF TOXICOLOGY
(2016)
Article
Cell Biology
Thomas Schwarz, Barbara Prieler, Johannes A. Schmid, Pawel Grzmil, Juergen Neesen
EUROPEAN JOURNAL OF CELL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Abdelghani Mazouzi, Federica Battistini, Sarah C. Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Juergen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I. Loizou
Article
Genetics & Heredity
Helga Rehder, Franco Laccone, Susanne G. Kircher, Ralf L. Schild, Christiane Rapp, Rainer Bald, Bernt Schulze, Jana Behunova, Juergen Neesen, Katharina Schoner
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2018)
Article
Multidisciplinary Sciences
Mira Stadler, Martin Scherzer, Stefanie Walter, Silvio Holzner, Karoline Pudelko, Angelika Riedl, Christine Unger, Nina Kramer, Beatrix Weil, Juergen Neesen, Markus Hengstschlaeer, Helmut Dolznig
SCIENTIFIC REPORTS
(2018)
Article
Biology
Zahida Parveen, Zohra Bibi, Nousheen Bibi, Juergen Neesen, Sajid Rashid
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Hannes Steinkellner, Julia Etzler, Laura Gogoll, Juergen Neesen, Eva Stifter, Oliver Brandau, Franco Laccone
EUROPEAN JOURNAL OF HUMAN GENETICS
(2015)
Article
Genetics & Heredity
Markus G. Seidel, Celia Duerr, Stavroula Woutsas, Anette Schwerin-Nagel, Kambis Sadeghi, Juergen Neesen, Sabine Uhrig, Elisangela Santos-Valente, Winfried F. Pickl, Wolfgang Schwinger, Christian Urban, Kaan Boztug, Elisabeth Foerster-Waldl
JOURNAL OF MEDICAL GENETICS
(2014)
Letter
Oncology
U. Platzbecker, F. Braulke, A. Kuendgen, K. Goetze, G. Bug, C. Schoenefeldt, K. Shirneshan, C. Roellig, M. Bornhaeuser, R. Naumann, J. Neesen, A. Giagounidis, W-K Hofmann, G. Ehninger, U. Germing, D. Haase, M. Wermke
Article
Genetics & Heredity
Philipp Velicky, Gudrun Meinhardt, Kerstin Plessl, Sigrid Vondra, Tamara Weiss, Peter Haslinger, Thomas Lendl, Karin Aumayr, Mario Mairhofer, Xiaowei Zhu, Birgit Schuetz, Roberta L. Hannibal, Robert Lindau, Beatrix Weil, Jan Ernerudh, Juergen Neesen, Gerda Egger, Mario Mikula, Clemens Roehrl, Alexander E. Urban, Julie Baker, Martin Knoefler, Juergen Pollheimer
Article
Genetics & Heredity
Mythily Ganapathi, Loukas Argyriou, Francisco Martinez-Azorin, Susanne Morlot, Gokhan Yigit, Teresa M. Lee, Bernd Auber, Alexander von Gise, Donald S. Petrey, Holger Thiele, Lukas Cyganek, Maria Sabater-Molina, Priyanka Ahimaz, Juan Cabezas-Herrera, Moises Sorli-Garcia, Arne Zibat, Markus D. Siegelin, Peter Burfeind, Christie M. Buchovecky, Gerd Hasenfuss, Barry Honig, Yun Li, Alejandro D. Iglesias, Bernd Wollnik
Article
Cell & Tissue Engineering
Sabine Rebs, Jakob Beier, Loukas Argyriou, Tillmann Schill, Gerd Hasenfuss, Dirk Vollmann, Samuel Sossalla, Katrin Streckfuss-Boemeke
Summary: AIC-iPSCs generated from a patient with arrhythmia-induced cardiomyopathy exhibit full pluripotency and differentiation characteristics, and can differentiate into functional beating cardiomyocytes, serving as a valuable cellular model for studying the molecular, genetic, and functional aspects of AIC.
STEM CELL RESEARCH
(2021)