Article
Clinical Neurology
R. G. Valencia, E. Mihailovska, L. Winter, K. Bauer, I Fischer, G. Walko, J. Jorgacevski, M. Potokar, R. Zorec, G. Wiche
Summary: P1c influences axonal microtubule dynamics through isoform-specific interaction with tubulin. Its deficiency in neurons affects microtubule dynamics, leading to altered neuritogenesis, neurite branching, growth cone morphology, and vesicles and mitochondria movement. On an organismal level, P1c deficiency results in impaired pain sensitivity, diminished learning capabilities, and reduced long-term memory in mice, indicating potential implications for cytoskeleton-related neuropathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Cell Biology
Lidia Bakota, Roland Brandt
Summary: Tau is a microtubule-associated protein that is enriched in the axonal process of neurons. This article discusses how the rapid interaction kinetics of tau with microtubules explains its lack of effect on axonal transport but ability to modulate microtubule polymerization. Additionally, tau modifications that slow down interaction kinetics can disrupt axonal transport and cause dendritic atrophy.
Article
Biochemistry & Molecular Biology
Mariya Genova, Lenka Grycova, Verena Puttrich, Maria M. Magiera, Zdenek Lansky, Carsten Janke, Marcus Braun
Summary: By using in-vitro reconstitution, this study reveals that the polyglutamylation generated by TTLL1 and TTLL7 differentially modulates the activities of Tau, katanin, and kinesin-1, providing mechanistic insight into how polyglutamylation selectively controls microtubule interactions in neurons.
Review
Cell Biology
Ana Catarina Costa, Monica Mendes Sousa
Summary: Neurons are polarized cells and the regulation of the microtubule cytoskeleton is crucial for their function. A group of microtubule-severing enzymes, including spastin, have been found to play an important role in regulating microtubule organization and axonal transport.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anu Antony, Neville Ng, Antonio Lauto, Jens R. Coorssen, Simon J. Myers
Summary: This study elucidated the crucial role of Ca2+-activated protease calpain in HSN1A, by regulating cellular cytoskeleton stability and microtubule transport function.
DNA AND CELL BIOLOGY
(2022)
Review
Endocrinology & Metabolism
Cunqing Yang, Xuefei Zhao, Xuedong An, Yuehong Zhang, Wenjie Sun, Yuqing Zhang, Yingying Duan, Xiaomin Kang, Yuting Sun, Linlin Jiang, Fengmei Lian
Summary: Diabetic peripheral neuropathy is a chronic metabolic disease that seriously affects patients' quality of life and can lead to amputation and neuropathic pain. Current treatment options only address symptoms and do not reverse nerve damage. Understanding the underlying mechanisms is crucial for prevention and the development of new therapies.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Cell Biology
Brittany MacTaggart, Anna Kashina
Summary: The cytoskeleton is essential for various cellular processes and its complexity is increased through posttranslational modifications, facilitating global and local cytoskeletal functions. Recent advancements in proteomics and cell biology have enabled the detailed study of individual PTMs and their role in the cytoskeleton.
Article
Neurosciences
Victorio M. Pozo Devoto, Valentina Lacovich, Monica Feole, Pratiksha Bhat, Jaroslav Chovan, Maria Carna, Isaac G. Onyango, Neda Dragisic, Martina Susserova, Martin E. Barrios-Llerena, Gorazd B. Stokin
Summary: Axonal swellings (AS) are neuropathological changes in several disorders, and their formation is associated with perturbed calcium homeostasis. Changes in intra-axonal calcium are not responsible for the formation of AS, but are required for their persistence. Following injury, the de/phosphorylation of axonal proteins, mainly those in the cytoskeleton, occurs, leading to rearrangement and support of axonal transport within AS.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell Biology
S. L. Morris, S. T. Brady
Summary: Tau, a phosphoprotein found in neurons, plays a major role in regulating fast axonal transport (FAT) through activation of neuronal signaling pathways. The exposure of tau PAD is an early event in tauopathies and is a major contributing factor to neurodegeneration. These findings suggest that the transient activation of the PP1-GSK3 β signaling pathway through locally regulated PAD exposure is crucial for cargo delivery and neurite outgrowth in developing neurons.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Endocrinology & Metabolism
Huimei Wei, Peng Huo, Shun Liu, Hua Huang, Shun Zhang
Summary: PCOS is a lifelong disorder affecting a significant number of women and associated with increased risk of various diseases. Posttranslational modifications play a crucial role in PCOS development, and understanding their roles and mechanisms can provide insights for future research and treatment.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Benjamin Combs, Kyle R. Christensen, Collin Richards, Andrew Kneynsberg, Rebecca L. Mueller, Sarah L. Morris, Gerardo A. Morfini, Scott T. Brady, Nicholas M. Kanaan
Summary: The study demonstrates that FTLD mutant tau proteins, P301L and R5L, can elicit a toxic effect on axonal transport as monomeric proteins. This suggests a mechanism of tau toxicity involving aberrant activation of a specific PP1 gamma-dependent pathway that disrupts axonal transport in neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Suresh Poudel, David Vanderwall, Zuo-Fei Yuan, Zhiping Wu, Junmin Peng, Yuxin Li
Summary: A computational pipeline JUMPptm was presented to extract PTMs from unenriched whole proteome. The deep brain proteome of Alzheimer's disease (AD) was analyzed using JUMPptm, revealing dysregulated PTM peptides during AD progression and establishing a valuable pan-PTM profile for AD research.
Article
Neurosciences
Alexander D. Law, Marlene Cassar, Dani M. Long, Eileen S. Chow, Jadwiga M. Giebultowicz, Anjana Venkataramanan, Roland Strauss, Doris Kretzschmar
Summary: This study investigates the molecular mechanisms of neurodegenerative diseases associated with Tau mutations using a Drosophila model. The results demonstrate that the disease phenotypes caused by Tau mutations involve both dominant and recessive effects, providing insights into the behavioral and molecular aspects of Tauopathies.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Takeshi Tsusaka, Juan A. Oses-Prieto, Christina Lee, Brian C. DeFelice, Alma L. Burlingame, Emily L. Goldberg
Summary: Ketone bodies are produced in the liver during glucose scarcity and act as alternative energy sources. Beta-hydroxybutyrate (BHB) has been identified as a signaling molecule, and lysine beta-hydroxybutyrylation (Kbhb) as a newly discovered post-translational modification. Kbhb is metabolically sensitive and found on proteins in multiple cellular compartments, suggesting its importance in ketone body-regulated physiology. However, caution is needed when using the H3K9bhb antibody to interpret gene regulation data, as it may recognize other modifications besides beta-hydroxybutyrylation.
Article
Cell Biology
Danila Di Meo, Priyadarshini Ravindran, Tanmay Sadhanasatish, Pratibha Dhumale, Andreas W. Puschel
Summary: During neuronal development, SadA/B kinases and AnkB regulate mitochondrial dynamics to maintain stability in axons and dendrites. Inhibition of SadA/B or AnkB leads to excessive fusion of mitochondria and activation of the integrated stress response. Mild actin destabilization can restore the normal dynamics of axonal mitochondria.
Review
Biochemistry & Molecular Biology
Heng Lin, Shon A. Koren, Gregor Cvetojevic, Peter Girardi, Gail V. W. Johnson
Summary: This research categorizes BAG3 studies into different clusters and highlights key findings in areas such as cancer, cardiomyopathy, neurodegeneration, and viral propagation. By analyzing protein mass spectrometry data and mutation information, it provides insights into the universal and cell-type-specific interactions of BAG3 and its functional implications.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Neurosciences
Heng Lin, Maoping Tang, Changyi Ji, Peter Girardi, Gregor Cvetojevic, Daniel Chen, Shon A. Koren, Gail V. W. Johnson
Summary: This study identified a novel BAG3-TBC1D10B-RAB35 regulatory axis that modulates protein degradation and tau clearance through the endosomal pathway, suggesting that dysregulation of BAG3 may contribute to the pathogenesis of AD.
BIOLOGICAL PSYCHIATRY
(2022)
Review
Cell Biology
Angie K. Torres, Bastian I. Rivera, Catalina M. Polanco, Claudia Jara, Cheril Tapia-Rojas
Summary: Normal aging results in decline of physiological functions, including cognitive impairment caused by synaptic dysfunction in the brain. Abnormal protein aggregates, such as phosphorylated tau protein, play a significant role in synaptic dysfunction and neurodegenerative diseases. Recent studies suggest that phosphorylated tau protein accumulates inside mitochondria, particularly in synaptic mitochondria, during normal aging, contributing to synaptic failure and cognitive impairment. Understanding the mechanisms leading to mitochondrial dysfunction and tau accumulation in synaptic mitochondria may provide potential therapeutic targets for age-related cognitive impairment.
NEURAL REGENERATION RESEARCH
(2022)
Review
Neurosciences
Heng Lin, Carol A. Deaton, Gail V. W. Johnson
Summary: This article discusses the mechanisms by which BAG3 regulates the vacuolar system and tau proteostasis, emphasizing the dysfunction of endosome-lysosome pathways in the accumulation of abnormal tau protein in neurodegenerative diseases. Overexpression of BAG3 decreases pathological tau levels and alleviates synapse loss in a tauopathy mouse model, and BAG3 interacts with key components of the vacuolar system such as clathrin and regulators of small GTPases. Therefore, BAG3 is an important regulator of endocytic pathways.
Article
Biochemistry & Molecular Biology
Francisca Villavicencio-Tejo, Margrethe A. Olesen, Alejandra Aranguiz, Rodrigo A. Quintanilla
Summary: Alzheimer's disease is characterized by memory and cognitive impairment, with the accumulation of amyloid beta-peptide and the presence of pathological forms of tau protein. Activation of the Nrf2 pathway has been found to protect against mitochondrial injury induced by pathological tau protein.
Article
Genetics & Heredity
Sanjib Guha, Anson Cheng, Trae Carroll, Dennisha King, Shon A. Koren, Sierra Swords, Keith Nehrke, Gail V. W. Johnson
Summary: Accumulation of inappropriately phosphorylated tau into neurofibrillary tangles is a defining feature of Alzheimer's disease. In this study, the researchers demonstrated the mechanisms through which the T231E mutation affects mitophagy, showing selectivity in its impact.
Review
Neurosciences
Margrethe A. Olesen, Francisca Villavicencio-Tejo, Rodrigo A. Quintanilla
Summary: Neurological disorders such as Alzheimer's disease and Parkinson's disease share common neuropathological signs, particularly mitochondrial abnormalities. Skin fibroblasts have been proposed as a useful tool to study early mitochondrial dysfunction in these diseases.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Biochemistry & Molecular Biology
Paloma P. Maldonado, Coram Guevara, Margrethe A. Olesen, Juan Andres Orellana, Rodrigo A. Quintanilla, Fernando C. Ortiz
Summary: This article discusses the role of mitochondrial dysfunction in the progression of multiple sclerosis (MS), focusing on the potential role of Nrf2 signaling in neuroinflammation and neurodegeneration. The authors propose that Nrf2 dysfunction affects the bioenergetics, antioxidant defense, and energy supply provided by glial cells to neurons.
Article
Biochemistry & Molecular Biology
Carolina A. Oliva, Daniela S. Rivera, Angie K. Torres, Carolina B. Lindsay, Cheril Tapia-Rojas, Francisco Bozinovic, Nibaldo C. Inestrosa
Summary: In Octodon degus, females experience more severe aging than males. Andrographolide treatment improves complex behaviors related to age-detrimental effects in females.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Francisca J. Allendes, Hugo S. Diaz, Fernando C. Ortiz, Noah J. Marcus, Rodrigo Quintanilla, Nibaldo C. Inestrosa, Rodrigo Del Rio
Summary: A significant number of COVID-19 survivors experience long-lasting cardiovascular sequelae associated with autonomic nervous system dysfunction, such as fatigue, arrhythmias, and hypertension. It is crucial to develop strategies for diagnosing and managing long-term health problems (long-COVID) due to the potential burden it can impose. Cardiovascular rehabilitation programs (CRPs) have shown promise in improving patient outcomes, and their application in treating the cardiovascular sequelae of long-COVID holds potential for enhancing functional capacity and quality of life.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Angie. K. K. Torres, Claudia Jara, Jesus Llanquinao, Matias Lira, Daniela Cortes-Diaz, Cheril Tapia-Rojas
Summary: Aging is a physiological process that leads to progressive decline in cellular functions. Mitochondrial dysfunction has been identified as a significant factor in aging, and specifically, the hippocampal mitochondria in aged female mice were found to exhibit various impairments in this study. These impairments include decreased bioenergetic function, increased ROS production, deregulation of calcium homeostasis, and disturbances in mitochondrial dynamics and quality control processes. These findings suggest that the accumulation of damaged mitochondria may contribute to the aging phenotype and age-related disabilities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jacen Emerson, Thomas Delgado, Peter Girardi, Gail V. W. Johnson
Summary: Astrocytes are important support cells in the central nervous system that affect the function and recovery of neurons. Reactive astrocytes can have both beneficial and harmful effects on injured neurons, and understanding the factors and pathways that determine their reactive phenotypes is still a developing field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Margrethe A. Olesen, Rodrigo A. Quintanilla
Summary: Tau protein is involved in various important functions in the central nervous system, such as maintaining cellular structure, facilitating axonal transport, and promoting synaptic communication. Studies have focused on understanding the role of tau modifications in Alzheimer's disease, particularly the cleavage of tau by caspases and its impact on neuronal function. Cleaved tau has been shown to contribute to oxidative damage, cognitive decline, and neurodegenerative manifestations in Alzheimer's disease. This review explores the significance of caspase-cleaved tau in the pathogenesis of Alzheimer's disease and its detrimental effects on neuronal function.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rodrigo G. Mira, Rodrigo A. Quintanilla, Waldo Cerpa
Summary: Traumatic brain injury (TBI) is brain damage caused by external forces. Mild TBI (mTBI) is the most common type of TBI and repeated mTBI increases the risk of neurodegenerative diseases. This study evaluated mitochondrial calcium dynamics in an mTBI mouse model using isolated hippocampal mitochondria. The findings showed that mTBI results in decreased mitochondrial membrane potential, increased basal matrix calcium levels, and increased NCLX protein levels.
Article
Biochemistry & Molecular Biology
Maria Jose Perez, Rodrigo Ibarra-Garcia-Padilla, Maoping Tang, George A. Porter Jr, Gail V. W. Johnson, Rodrigo A. Quintanilla
Summary: The cleavage of tau protein by Caspase-3 negatively affects mitochondrial bioenergetics through the activation of mitochondrial permeability transition pore (mPTP), emphasizing the importance of this channel and its regulatory protein, cyclophilin D (CypD), in neuronal damage induced by tau pathology in Alzheimer's disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)