Article
Biochemistry & Molecular Biology
Alisa Cario, Christopher L. Berger
Summary: The etiology of Tauopathies is usually explained by Tau dysfunction leading to loss of axonal microtubule stability. However, Tau has multiple functions beyond regulating microtubule dynamics, including modulating motor proteins, acting as a signaling hub, and serving as a scaffolding protein. Due to the dynamic nature of Tau isoform expression, post-translational modifications, and conformational flexibility, there is no single mechanism to describe Tau dysfunction. Studying the effects of specific pathogenic mutations or aberrant modifications on all of Tau's functions is essential to understand the unique etiology of each disease state.
Article
Neurosciences
Elizabeth L. Steuer, Lisa J. Kemper, Chris J. W. Hlynialuk, Kailee Leinonen-Wright, Michelle L. Montonye, Ian P. Lapcinski, Colleen L. Forster, Karen H. Ashe, Peng Liu
Summary: A study on genetically matched htau targeted-insertion mouse lines shows that blocking htau cleavage at D314 can delay neurodegeneration and cognitive deficits associated with frontotemporal dementia (FTD), providing insights into the pathology and potential treatments for dementia.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Samanta Mazzetti, Alessandra M. Calogero, Gianni Pezzoli, Graziella Cappelletti
Summary: This paragraph discusses the interplay between alpha-synuclein and the microtubule cytoskeleton in neurodegenerative diseases. Alpha-synuclein is a key protein involved in neurodegeneration, and its interaction with other proteins and structures makes it difficult to identify the trigger for neuronal death. The imbalance of the microtubule cytoskeleton is emerging as a convergence point in neurodegeneration. Alpha-synuclein and microtubules have been shown to interact and communicate with other intracellular structures.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Endocrinology & Metabolism
Tibor Szenasi, Gabor Turu, Laszlo Hunyady
Summary: beta-arrestins, initially known for their role in desensitizing rhodopsin and other G protein-coupled receptors, interact with the cytoskeletal system, including microtubules, actin filaments, and intermediate filaments. They regulate the activity of microtubules by recruiting signaling proteins and interacting with assembly proteins that control the actin cytoskeleton and intermediate filaments. Dysregulation of the cytoskeletal system is implicated in the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's. Therefore, beta-arrestins are potential targets for future treatments of these diseases.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Giulia Montalto, Roberta Ricciarelli
Summary: Tau is a macrotubule-associated protein that plays a crucial role in stabilizing the cytoskeleton. While phosphorylation normally decreases tau's affinity for microtubules, hyperphosphorylated tau forms aggregates that contribute to the development of neurofibrillary tangles in Alzheimer's disease and other tauopathies. This review provides an overview of tau's structure and the pathophysiological effects of tau phosphorylation, as well as the progress in developing drug therapies targeting tau kinases.
Article
Neurosciences
Riccardo Zocchi, Emanuele Bellacchio, Michela Piccione, Raffaella Scardigli, Valentina D'Oria, Stefania Petrini, Kristin Baranano, Enrico Bertini, Antonella Sferra
Summary: In this study, a previously unreported missense mutation p.I384N in TUBA1A gene is causally linked to a neurodegenerative disorder characterized by progressive spastic paraplegia and ataxia. The mutation impairs TUBA1A stability and prevents its incorporation into microtubules. The inhibition of proteasome degradative systems increases the protein levels of TUBA1A mutant and promotes the formation of tubulin aggregates.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Neurosciences
Graziella Cappelletti, Alessandra Maria Calogero, Chiara Rolando
Summary: This study discusses the importance of microtubule acetylation in controlling neuronal and glial function, as well as its role in neurodegenerative disorders. Research has found that microtubule acetylation is a key modification that controls intracellular transport and stability, potentially serving as a novel therapeutic intervention for diseases like Parkinson's.
NEUROSCIENCE LETTERS
(2021)
Review
Neurosciences
Siwei Chu, Xinyi Xie, Carla Payan, Ursula Stochaj
Summary: The AAA(+) ATPase valosin containing protein (VCP) is crucial for maintaining the stability of cells and organs, especially in the nervous system. VCP collaborates with various cofactors to ensure proteostasis and is linked to human health through numerous mutations. Dysfunctional VCP is associated with neurodegeneration and other diseases, as it is responsible for dismantling protein aggregates and removing dysfunctional organelles. Further research is needed to uncover the molecular mechanisms connecting VCP mutations to specific brain pathologies and explore its potential as a drug target for neurodegeneration.
MOLECULAR NEURODEGENERATION
(2023)
Article
Multidisciplinary Sciences
Dong Jin Mun, Bon Seong Goo, Bo Kyoung Suh, Ji-Ho Hong, Youngsik Woo, Soo Jeong Kim, Seunghyun Kim, Su Been Lee, Yubin Won, Jin Yeong Yoo, Eunbyul Cho, Eun Jin Jang, Truong Thi My Nhung, Hong Minh Triet, Hongyul An, Haeryun Lee, Minh Dang Nguyen, Seung-Yeol Park, Seung Tae Baek, Sang Ki Park
Summary: In this study, the Gcap14-Ndel1 complex is identified as a fundamental regulator of cytoskeletal remodeling during neurodevelopment, including neuronal process elongation and migration. Deficiency of Gcap14 leads to impaired cortical lamination and defective neuronal migration. The interaction between Gcap14 and Ndel1 effectively corrects the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Cell Biology
Dan Ohtan Wang
Summary: Functional genomics and systems biology have provided new approaches for studying gene and protein networks in the central nervous system. Current research is uncovering the connection between brain function and gene regulation, particularly in the field of epitranscriptomics. However, there is still much to learn about these complex regulatory mechanisms.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ibtissem Nabti, Babu J. N. Reddy, Rachid Rezgui, Wenqi Wang, Steven P. Gross, George T. Shubeita
Summary: This study demonstrates that phosphorylated MAP4 can bias organelle transport towards the microtubule minus-ends by impairing the force generation of kinesin-1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Lukas Seebauer, Yanni Schneider, Alice Drobny, Sonja Ploetz, Tomas Koudelka, Andreas Tholey, Iryna Prots, Beate Winner, Friederike Zunke, Juergen Winkler, Wei Xiang
Summary: In this study, the impact of aSyn on microtubule organization was investigated in cell models and patient-derived neurons. The results suggest that aSyn aggregation interferes with microtubule organization, leading to impaired neuritic phenotypes in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Amy N. Zwierzchowski-Zarate, Ayde Mendoza-Oliva, Omar M. Kashmer, Josue E. Collazo-Lopez, Charles L. White, Marc Diamond
Summary: Tau aggregation is the basis of neurodegenerative tauopathies, and RNA may play an important role in this process. This study found that human RNA specifically induces the formation of stable tau strains and may trigger the formation of pathological assemblies in Alzheimer's disease and other tauopathies. These findings are of significant importance for understanding the pathological mechanisms of tauopathies and developing related therapeutic strategies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Cell Biology
Debora Bencivenga, Emanuela Stampone, Domenico Roberti, Fulvio Della Ragione, Adriana Borriello
Summary: p27(Kip1) plays a crucial role in cell cycle regulation, with additional functions in cell motility, differentiation, apoptosis, and other processes. Its activities are modulated by factors such as level, localization, and post-translational modifications.
Review
Cell Biology
Ping Zhou, Guiwen Yang, Wei Xie
Summary: The remodeling of microtubules during cell differentiation is a critical process that involves microtubule-binding proteins, cell junctions, and centrosomes. Recent studies have shed light on the dynamic changes in microtubule organization and functions during cell differentiation, revealing the regulatory mechanisms and physiological functions of this process.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Matthias Schiedel, Tobias Rumpf, Berin Karaman, Attila Lehotzky, Stefan Gerhardt, Judit Ovadi, Wolfgang Sippl, Oliver Einsle, Manfred Jung
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2016)
Review
Biochemical Research Methods
Judit Olah, Philippe Bertrand, Judit Ovadi
EXPERT REVIEW OF PROTEOMICS
(2017)
Article
Chemistry, Medicinal
Matthias Schiedel, Daniel Herp, Soeren Hammelmann, Soeren Swyter, Attila Lehotzky, Dina Robaa, Judit Olah, Judit Ovadi, Wolfgang Sippl, Manfred Jung
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Robert G. Tripon, Judit Olah, Tajwar Nasir, Lajos Csincsik, Chee Lok Li, Sandor Szunyogh, Haiyan Gong, Jane M. Flinn, Judit Ovadi, Imre Lengyel
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2018)
Article
Biology
Soeren Swyter, Matthias Schiedel, Daria Monaldi, Sandor Szunyogh, Attila Lehotzky, Tobias Rumpf, Judit Ovadi, Wolfgang Sippl, Manfred Jung
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2018)
Article
Multidisciplinary Sciences
J. Olah, T. Szenasi, S. Szunyogh, A. Szabo, A. Lehotzky, J. Ovadi
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Adel Szabo, Judit Olah, Sandor Szunyogh, Attila Lehotzky, Tibor Szenasi, Marianna Csaplar, Matthias Schiedel, Peter Low, Manfred Jung, Judit Ovadi
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Judit Olah, Judit Ovadi
Article
Biochemistry & Molecular Biology
Judit Olah, Sandor Szunyogh, Tibor Szenasi, tamas Szaniszlo, Adel Szabo, Attila Lehotzky, Timea Berki, Laszlo Nyitray, Judit Ovadi
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2019)
Review
Cell Biology
Judit Olah, Attila Lehotzky, Sandor Szunyogh, Tibor Szenasi, Ferenc Orosz, Judit Ovadi
Review
Cell Biology
Victor Norris, Judit Ovadi
Summary: The emergence of the novel coronavirus SARS-CoV-2 has caused significant healthcare and socioeconomic problems worldwide, with uncertainties surrounding its rapid spread and severe health impacts. While progress is being made in developing vaccines and medications, the appearance of new, more aggressive mutants poses challenges for treatment.
Review
Biochemistry & Molecular Biology
Judit Olah, Tibor Szenasi, Attila Lehotzky, Victor Norris, Judit Ovadi
Summary: Protein-protein interactions (PPIs) play a crucial role in fundamental processes and are associated with pathological conditions. However, discovering drugs that can modulate PPIs poses challenges and limitations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Judit Olah, Attila Lehotzky, Tibor Szenasi, Judit Ovadi
Summary: DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson's disease by inhibiting the toxic assembly of SYN promoted by TPPP/p25. The interaction of DJ-1 with TPPP/p25 hinders the pathology of SYN with TPPP/p25, leading to decreased intracellular fluorescence and increased proteolytic degradation of SYN complexed with TPPP/p25. This study reveals a new protective function of DJ-1 against toxic SYN assemblies in living human cells.
Article
Cell Biology
Judit Olah, Attila Lehotzky, Tibor Szenasi, Timea Berki, Judit Ovadi
Summary: TPPP3, similar to TPPP1, modulates microtubule organization but does not bind to SYN, thus inhibiting SYN aggregation and potentially serving as an agent for developing anti-Parkinson's drugs.
Article
Biochemistry & Molecular Biology
Tibor Szenasi, Judit Olah, Adel Szabo, Sandor Szunyogh, Andras Lang, Andras Perczel, Attila Lehotzky, Vladimir N. Uversky, Judit Ovadi
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2017)