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)
Article
Multidisciplinary Sciences
Sebastian J. Baumann, Julia Grawenhoff, Elsa C. Rodrigues, Silvia Speroni, Maria Gili, Artem Komissarov, Sebastian P. Maurer
Summary: Understanding where mRNAs are translated in the cytoplasm is crucial for protein expression. In this study, researchers discover that APC acts as an adaptor for kinesin-based mRNA transport, forming stable complexes with neuronal mRNA fragments. The interaction between APC-RNPs and kinesin-1 enables highly processive mRNA transport along microtubules, and the presence of end-binding protein 1 (EB1) facilitates dynamic movement of APC-RNPs. These findings establish the importance of APC in the bidirectional movement of neuronal transport mRNPs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Laia Lidon, Laura Llao-Hierro, Mario Nuvolone, Adriano Aguzzi, Jesus avila, Isidro Ferrer, Jose Antonio del Rio, Rosalina Gavin
Summary: Through research on AD patient samples and mouse models, it was found that there is a parallel association between PrPC and the 4R isoforms of tau protein. Reducing or eliminating PrPC levels leads to an increase in the balance of tau protein 3R/4R.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Galina Limorenko, Hilal A. Lashuel
Summary: The study explores the effects of heparin on Tau aggregation and provides new insights into its role in Tauopathies. The review calls for a reassessment of approaches to studying Tau aggregation mechanisms, development of better diagnostic tools to enhance understanding of Tauopathies, and more effective means for drug development.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Neurosciences
Felix Hernandez, Isidro Ferrer, Mar Perez, Juan Carlos Zabala, Jose Antonio del Rio, Jesus Avila
Summary: This article reexamines the aggregation of tau protein at primary, secondary, tertiary, and quaternary structures. Additionally, the presence of non-aggregated tau protein, which has been recently discovered, is also discussed.
Article
Clinical Neurology
Kanta Horie, Nicolas R. Barthelemy, Chihiro Sato, Randall J. Bateman
Summary: The study analyzed MTBR-Tau species in Alzheimer's disease and control CSF using sequential immunoprecipitation and chemical extraction methods followed by mass spectrometry. The species containing the region beginning at residue 243 were found to be highly correlated with tau PET and cognitive measures. This suggests that CSF level of tau species containing the upstream region of MTBR may serve as biomarkers to stage Alzheimer's disease and track the development of tau-directed therapeutics.
Article
Clinical Neurology
Kanta Horie, Nicolas R. Barthelemy, Chihiro Sato, Randall J. Bateman
Summary: The study analyzed MTBR-tau species in CSF and found that tau species containing the upstream region of MTBR were highly correlated with tau PET and cognitive assessments in Alzheimer's disease, suggesting they could serve as biomarkers for staging Alzheimer's disease and tracking tau-directed therapeutics development.
Article
Biochemistry & Molecular Biology
Hilda Mirbaha, Dailu Chen, Vishruth Mullapudi, Sandi Jo Terpack, Charles L. White, Lukasz A. Joachimiak, Marc Diamond
Summary: The study reveals that the initiation of tauopathy is associated with the formation of seed-competent (M-s) tau monomers, which precedes the formation of insoluble fibrils. This research provides important insights into the origins of tauopathy and highlights the significance of M-s monomers in disease progression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hilda Mirbaha, Dailu Chen, Vishruth Mullapudi, Sandi Jo Terpack, Charles L. White, Lukasz A. Joachimiak, Marc Diamond
Summary: The research shows that in a mouse model of tauopathy, the disease begins with the formation of M-s monomers, whose conformational activity is independent of phosphorylation, and forms oligomers before further assembling into insoluble fibrils.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Galina Limorenko, Meltem Tatli, Rajasekhar Kolla, Sergey Nazarov, Marie-Theres Weil, David C. Schondorf, Daniela Geist, Peter Reinhardt, Dagmar E. Ehrnhoefer, Henning Stahlberg, Laura Gasparini, Hilal A. Lashuel
Summary: The authors present a method to produce co-factor-free fibrils from all full-length Tau isoforms, which allows for the reconstitution of pathology resembling Tau fibrils and the screening of Tau aggregation-modifying compounds for targeted therapies and PET tracers.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Cyntha M. van den Berg, Vladimir A. Volkov, Sebastian Schnorrenberg, Ziqiang Huang, Kelly E. Stecker, Ilya Grigoriev, Sania Gilani, Kari-Anne M. Frikstad, Sebastian Patzke, Timo Zimmermann, Marileen Dogterom, Anna Akhmanova
Summary: CSPP1, a protein associated with cilia and centrosomes, preferentially binds to slowly growing or perturbed microtubule ends, stabilizing their structure. This study reveals the mechanisms by which CSPP1 regulates the elongation and stability of cilia and other microtubule-based structures by inhibiting microtubule growth and shortening.
JOURNAL OF CELL BIOLOGY
(2023)
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
Biology
Miao Chen, Jian Wang, Yang Yang, Tao Zhong, Peng Zhou, Huixian Ma, Jingrui Li, Dengwen Li, Jun Zhou, Songbo Xie, Min Liu
Summary: Cytoskeletal protein EB1 is susceptible to glutathionylation under oxidizing conditions, which helps control its activity and protect it from oxidative damage. This glutathionylation of EB1 plays a crucial role in regulating microtubule dynamics and cellular activities.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lan Liu, Xuemin Chen, Jun Li, Huaibin Wang, Christopher J. Buehl, Noah J. Goff, Katheryn Meek, Wei Yang, Martin Gellert
Summary: DNA-PK plays a dual role in DNA damage repair by protecting and processing broken DNA ends. The type of DNA ends regulates the kinase activity and autophosphorylation of DNA-PK, which in turn coordinate non-homologous end joining (NHEJ) events.
Article
Physics, Applied
Milan Vala, David Palounek, Hadrien M. L. Robert, Marek Piliarik
Summary: This study quantifies the scattering anisotropy of single unlabeled microtubules with high precision using polarization-sensitive microscopy. The research explains the structural origin of microtubule anisotropy and monitors the impact of tau protein binding on microtubules.
JOURNAL OF PHYSICS D-APPLIED PHYSICS
(2021)
Review
Cell Biology
Chadni Sanyal, Niels Pietsch, Sacnicte Ramirez Rios, Leticia Peris, Lucie Carrier, Marie-Jo Moutin
Summary: Among various post-translational modifications of microtubules, the detyrosination/re-tyrosination cycle specifically occurs in tubulin. This cycle involves enzymatic removal and re-addition of a tyrosine residue at the C-terminus of alpha-tubulin, and also the conversion of detyrosinated tubulin to Delta 2-tubulin. The cycle regulates microtubule dynamics and cargo trafficking, and plays a crucial role in neuronal health and heart function. Dysregulation of the cycle is associated with neurodegeneration and heart failure in humans.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Neurosciences
Alejandro Anton-Fernandez, Laura Valles-Saiz, Jesus Avila, Felix Hernandez
Summary: Tau protein is mainly localized in the cytoplasm of neuronal cells but can also be found in the cell nucleus, where it binds to nucleic acids. The increase in nuclear tau during aging may contribute to the activation of transposons and accelerate aging.
Article
Clinical Neurology
Rocio Alfaro-Ruiz, Carolina Aguado, Alejandro Martin-Belmonte, Ana Esther Moreno-Martinez, Jesus Merchan-Rubira, Felix Hernandez, Jesus Avila, Yugo Fukazawa, Rafael Lujan
Summary: N-methyl-D-aspartate receptors are important in Alzheimer's disease, and their expression and localization differ at synaptic and extrasynaptic sites, which is associated with accumulation of phospho-tau.
Article
Neurosciences
Anne Fourest-Lieuvin, Angelique Vinit, Beatrice Blot, Anthime Perrot, Eric Denarier, Isabelle Arnal
Summary: In this study, researchers developed a method to induce controlled cleavage of the tau protein at specific sites. They found that the resulting tau fragments had different interactions with cellular structures, particularly the cytoskeleton. Some cleavages at specific amino acid positions displayed cellular toxicity and unusual relocalization of the fragment.
Article
Cell Biology
Laurence Serre, Julie Delaroche, Angelique Vinit, Guy Schoehn, Eric Denarier, Anne Fourest-Lieuvin, Isabelle Arnal
Summary: Adenomatous polyposis coli (APC), a scaffold protein with tumor suppressor properties, plays important roles in mitosis and cytoskeleton regulation. This study investigated the molecular mechanisms of APC-C, the C-terminal domain of APC, in microtubule regulation. It was found that APC-C promotes both microtubule growth and shrinkage and accumulates at shrinking microtubule extremities. Cryo-electron microscopy revealed that APC-C adopts an extended conformation along the protofilament crest and decorates microtubules with ring-like tubulin oligomers. Furthermore, APC-C's interaction with microtubules is essential for correct mitotic chromosome alignment. These findings suggest that the bilateral interaction of APC-C with tubulin and microtubules contributes to its mitotic functions.
JOURNAL OF CELL SCIENCE
(2023)
Article
Oncology
Remi Eyraud, Stephane Ayache, Philipp. O. O. Tsvetkov, Shanmugha Sri Kalidindi, Viktoriia. E. E. Baksheeva, Sebastien Boissonneau, Carine Jiguet-Jiglaire, Romain Appay, Isabelle Nanni-Metellus, Olivier Chinot, Francois Devred, Emeline Tabouret
Summary: Plasma denaturation profiles obtained through nanoDSF can be used with AI algorithms to discriminate EGFR alterations in glioblastoma (GBM), providing a predictive diagnostic biomarker for therapy strategies.
Article
Biochemistry & Molecular Biology
Viktoriia E. Baksheeva, Veronika V. Tiulina, Elena N. Iomdina, Sergey Yu. Petrov, Olga M. Filippova, Nina Yu. Kushnarevich, Elena A. Suleiman, Remi Eyraud, Francois Devred, Marina V. Serebryakova, Natalia G. Shebardina, Dmitry V. Chistyakov, Ivan I. Senin, Vladimir A. Mitkevich, Philipp O. Tsvetkov, Evgeni Yu. Zernii
Summary: Primary open-angle glaucoma (POAG) is a common neurodegenerative disorder that causes blindness and is characterized by optic nerve and retinal ganglion cell damage. Early detection and treatment of the disease are crucial, but difficult due to its asymptomatic nature and lack of objective diagnostic approaches. Recent studies have shown that glaucoma involves complex metabolomic and proteomic changes in eye liquids, including tear fluid. However, the analysis of tear fluid is technically challenging and not suitable for clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Natalia Molinero, Alejandro Anton-Fernandez, Falix Hernandez, Jesus Avila, Begona Bartolome, M. Victoria Moreno-Arribas
Summary: Gut microbiota is a diverse population of microorganisms in the gastrointestinal tract that influences host health and disease. Age is a conditioning factor for the vitality of the gut microbiota, and aging is a primary risk factor for neurodegenerative diseases like Alzheimer's disease (AD). This paper summarizes the emerging evidence on the link between the oral and gut microbiome and neurodegeneration, with a focus on AD.
Article
Biochemistry & Molecular Biology
Laura Valles-Saiz, Jesus avila, Felix Hernandez
Summary: The dysregulation of transposable elements is involved in neurodegenerative disorders. This study investigated the protective effects of the reverse transcriptase inhibitor lamivudine in a mouse model of Alzheimer's disease. The results showed that lamivudine treatment reduced histopathological markers of tauopathies and improved motor and cognitive functions. Additional experiments revealed that tau promotes the insertion of transposable elements, and lamivudine inhibits this insertion. These findings suggest that early administration of lamivudine may attenuate the progression of tauopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Di Ma, Chao Sun, Rahul Manne, Tianqi Guo, Christophe Bosc, Joshua Barry, Thomas Magliery, Annie Andrieux, Houzhi Li, Chen Gu
Summary: This study suggests that the dysfunctions of MAP6 and Kv3.1 channels are associated with the pathogenesis of schizophrenia. MAP6 stabilizes Kv3.1 channels in PV+ neurons and plays a role in behavioral regulation. Decreased levels of MAP6 or Kv3.1 protein result in behavior abnormalities similar to schizophrenia.
MOLECULAR PSYCHIATRY
(2023)
Article
Hematology
Alexei Grichine, Shancy Jacob, Anita Eckly, Joran Villaret, Clotilde Joubert, Florence Appaix, Mylene Pezet, Anne-Sophie Ribba, Eric Denarier, Jacques Mazzega, Jean-Yves Rinckel, Laurence Lafanechere, Benedicte Elena-Herrmann, Jesse W. Rowley, Karin Sadoul
Summary: Blood platelets undergo cytoskeleton reorganizations during vessel injury, and expanding platelets have increased mitochondria and experience mitochondrial fission. Drp1-deficient platelets show a defect in clot retraction.
Article
Neurosciences
Indalo Domene-Serrano, Raquel Cuadros, Felix Hernandez, Jesus Avila, Ismael Santa-Maria
Summary: This study accurately predicted, analyzed, and understood tau protein structure and the conformational basis for the neuroprotective role of W-tau using a tridimensional deep learning-based approach and in vitro polymerization assay. The findings demonstrate the importance of the structure-function relationship on the neuroprotective behavior of W-tau inhibiting tau fibrillization in vitro.
JOURNAL OF ALZHEIMERS DISEASE REPORTS
(2023)