Article
Clinical Neurology
Juan Carlos Polanco, Gabriel Rhys Hand, Adam Briner, Chuanzhou Li, Jurgen Gotz
Summary: The study revealed that tau seeds in tauopathies spread trans-synaptically via exosomes, escaping endosomes through lysosomal degradation to induce tau aggregation in the cytosol. The enzymatic activities of lysosomes permeabilize exosomal and endosomal membranes, facilitating access of exosomal tau seeds to cytosolic tau for aggregation. This highlights the crucial role of endosomal membrane integrity in cellular invasion by misfolded proteins resistant to lysosomal degradation.
ACTA NEUROPATHOLOGICA
(2021)
Article
Cell Biology
Nicholas Ariotti, Yeping Wu, Satomi Okano, Yann Gambin, Jordan Follett, James Rae, Charles Ferguson, Rohan D. Teasdale, Kirill Alexandrov, Frederic A. Meunier, Michelle M. Hill, Robert G. Parton
Summary: CAV1 can be secreted in an inverted form from specific types of prostate cancer cells, and released through a non-canonical autophagy pathway, representing a novel class of exosomes.
Article
Multidisciplinary Sciences
Yin Xu, Nicholas E. Propson, Shuqi Du, Wen Xiong, Hui Zheng
Summary: Studies indicate that microglial-specific autophagy, represented by Atg7, plays a crucial role in regulating lipid metabolism and neuroinflammation. Deletion of Atg7 in microglia leads to a proinflammatory status and exacerbates intraneuronal tau pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Lauren H. Fairley, Imane Lejri, Amandine Grimm, Anne Eckert
Summary: Abnormal tau build-up is a hallmark of Alzheimer's disease and other neurodegenerative diseases. Mitochondrial dysfunction is associated with tau pathology. This study investigated the effects of spermidine, a neuroprotective polyamine, on mitochondrial function in a cellular model of tauopathy. The results showed that spermidine improved mitochondrial function and restored tau-induced impairments in mitophagy, suggesting that spermidine supplementation might be a potential therapeutic approach for tau-related mitochondrial impairments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Toxicology
Rong-Jane Chen, Yu-Hsuan Lee, Tzu-Hao Chen, Yu-Ying Chen, Ya-Ling Yeh, Ching-Ping Chang, Chien-Cheng Huang, How-Ran Guo, Ying-Jan Wang
Summary: Carbon monoxide, known as a silent killer, can reduce oxygen carrying capacity in the body by binding to hemoglobin. While toxic at high concentrations, CO has cyto- and tissue-protective effects at low concentrations, modulating inflammatory responses through regulation of cytokine production. Understanding the interplay between mitochondria, autophagy, exosomes, and the inflammasome is crucial for understanding the health effects of CO and potential treatment strategies for inflammation-related diseases.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Medicine, Research & Experimental
Shiyin Lin, Tian Meng, Haofeng Huang, Haixia Zhuang, Zhengjie He, Huan Yang, Du Feng
Summary: Membrane contact sites are regions where two different organelles are closely apposed and communicate through protein-protein or protein-lipid interactions. These contacts play a crucial role in mediating substance exchange and signal transduction within cells. The endoplasmic reticulum, as the largest reticulum network in the cell, communicates extensively with other organelles through various protein tethers and lipids, facilitating the transport of ions, lipids, and proteins between organelles.
Article
Neurosciences
Erin T. Williams, Xi Chen, P. Anthony Otero, Darren J. Moore
Summary: Perturbations of the endolysosomal pathway, specifically involving VPS35 and the retromer complex, play an important role in the pathogenesis of Parkinson's disease and Alzheimer's disease. This review focuses on the impact of the PD-linked D620N mutation in causing retromer dysfunction and its implications in neurodegeneration. The association of VPS35 and the retromer with other neurodegenerative diseases is also discussed.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Geriatrics & Gerontology
Sara Cazzaro, Cenxiao Fang, Hirah Khan, Richard Witas, Teresa R. Kee, Jung-A A. Woo, David E. Kang
Summary: The study reveals that cargo receptors Sqstm1/p62 and optineurin inhibit sEV secretion, which requires their ability to bind ubiquitinated cargo. In addition, increasing actin dynamics can also enhance sEV secretion. These findings provide a potential strategy to promote misfolded protein degradation and reduce sEV-mediated cell-to-cell spread of pathology.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Editorial Material
Cell Biology
Somya Vats, Thierry Galli
Summary: SERP, a secretory mechanism bypassing the Golgi apparatus, plays a crucial role in releasing ER elements and promoting neurite growth. In the absence of macroautophagy, SERP becomes more efficient in promoting secretion of specific proteins and altering neuronal polarity.
Review
Biochemistry & Molecular Biology
Juan Carlos Polanco, Jurgen Gotz
Summary: The study investigates the propagation mechanisms of tau seeds in Alzheimer's disease and proposes potential methods to control their spread by manipulating mechanisms. It emphasizes the ability of tau seeds to trigger endolysosomal permeabilization and suggests targeting the endolysosomal pathway as a key to developing broad-spectrum treatments for neurodegenerative diseases.
Article
Multidisciplinary Sciences
Shu Liu, Andre Hossinger, Stefanie-Elisabeth Heumuller, Annika Hornberger, Oleksandra Buravlova, Katerina Konstantoulea, Stephan A. Muller, Lydia Paulsen, Frederic Rousseau, Joost Schymkowitz, Stefan F. Lichtenthaler, Manuela Neumann, Philip Denner, Ina M. Vorberg
Summary: Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. The study shows that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes.
NATURE COMMUNICATIONS
(2021)
Review
Geriatrics & Gerontology
Lukasz Zadka, Marta Sochocka, Naomi Hachiya, Justyna Chojdak-Lukasiewicz, Piotr Dziegiel, Egbert Piasecki, Jerzy Leszek
Summary: Alzheimer's disease is a neurodegenerative disorder with unclear pathogenesis. Previous research suggests that endolysosomal abnormalities play a crucial role in causing brain lesions.
Article
Cell Biology
Cenxiao Fang, Jung-A A. Woo, Tian Liu, Xingyu Zhao, Sara Cazzaro, Yan Yan, Jenet Matlack, Teresa Kee, Patrick LePochat, David E. Kang
Summary: The study reveals that SSH1, a canonical CFL phosphatase, dephosphorylates phospho-Ser403-SQSTM1, impairing SQSTM1 flux and phospho-MAPT/tau clearance. This unique action of SSH1 on SQSTM1 is separate from CFL activation and suggests an inhibitory role of SSH1 in autophagic cargo clearance.
Article
Pharmacology & Pharmacy
H-F Wei, S. Anchipolovsky, R. Vera, G. Liang, D-M Chuang
Summary: Lithium can inhibit Ca2+ dysregulation and associated pathology in both Alzheimer's disease and COVID-19, making it a potential treatment option for patients with these diseases.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Xu Hou, Jens O. Watzlawik, Casey Cook, Chia-Chen Liu, Silvia S. Kang, Wen-Lang Lin, Michael DeTure, Michael G. Heckman, Nancy N. Diehl, Fadi S. Hanna Al-Shaikh, Ronald L. Walton, Owen A. Ross, Heather L. Melrose, Nilufer Ertekin-Taner, Guojun Bu, Leonard Petrucelli, John D. Fryer, Melissa E. Murray, Dennis W. Dickson, Fabienne C. Fiesel, Wolfdieter Springer
Summary: The study reveals alterations in mitophagy in AD that are associated with early tau pathology, suggesting that distinct mitochondrial, autophagic, and/or lysosomal failures may contribute to the selective vulnerability in the disease.
ALZHEIMERS & DEMENTIA
(2021)