Article
Neurosciences
Emily E. Handley, Laura A. Reale, Jyoti A. Chuckowree, Marcus S. Dyer, Grace L. Barnett, Courtney M. Clark, William Bennett, Tracey C. Dickson, Catherine A. Blizzard
Summary: Estrogen plays a significant role in mitigating disease progression and pathogenesis in ALS, by influencing spine density and plasticity, resulting in improved disease severity and outcomes.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Giada Zanini, Valentina Selleri, Milena Nasi, Anna De Gaetano, Ilaria Martinelli, Giulia Gianferrari, Francesco Demetrio Lofaro, Federica Boraldi, Jessica Mandrioli, Marcello Pinti
Summary: This study reports the clinical and biological features of an ALS patient with pA382T mutation in TPD-43 protein. The mutation leads to significant alterations in neuronal proteome, particularly impacting mitochondrial metabolic pathways and the endoplasmic reticulum. The findings suggest that mitochondrial dysfunction and misplacement of mitochondrial DNA may be mechanisms contributing to ALS caused by this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Hadjara Sidibe, Yousra Khalfallah, Shangxi Xiao, Nicolas B. Gomez, Hana Fakim, Elizabeth M. H. Tank, Genevieve Di Tomasso, Eric Bareke, Anais Aulas, Paul M. McKeever, Ze'ev Melamed, Laurie Destroimaisons, Jade-Emmanuelle Deshaies, Lorne Zinman, J. Alex Parker, Pascale Legault, Martine Tetreault, Sami J. Barmada, Janice Robertson, Christine Vande Velde
Summary: The study reveals that TDP-43 stabilizes G3BP1 transcripts, nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels, and G3BP1 transcripts are reduced in neurons of ALS/FTD patients with TDP-43 cytoplasmic inclusions/nuclear depletion. These findings suggest that loss of function of TDP-43 and G3BP1 may contribute to ALS/FTD pathogenesis.
Article
Clinical Neurology
Yuting Ren, Siyuan Li, Siyu Chen, Xiaosun Sun, Fei Yang, Hongfen Wang, Mao Li, Fang Cui, Xusheng Huang
Summary: The levels of plasma TDP-43 and pTDP-43 were significantly higher in ALS patients compared to healthy controls, with plasma TDP-43 showing high sensitivity and specificity in differentiating between the two groups and indicating disease progression.
FRONTIERS IN NEUROLOGY
(2021)
Article
Geriatrics & Gerontology
Zhe Long, Muireann Irish, John R. Hodges, Glenda Halliday, Olivier Piguet, James R. Burrell
Summary: Clinical and pathological heterogeneity is common in patients with frontotemporal lobar degeneration (FTLD) pathology. Characteristics that differentiate between FTLD-TDP and FTLD-tau, as well as different subtypes within FTLD-TDP, were investigated. Amyotrophic lateral sclerosis features were highly specific for FTLD-TDP, which showed greater atrophy than FTLD-tau. TDP-43 subtyping may have more clinical utility in distinguishing different profiles within FTLD-TDP.
NEUROBIOLOGY OF AGING
(2021)
Review
Neurosciences
Sarah Lepine, Maria Jose Castellanos-Montiel, Thomas Martin Durcan
Summary: The abnormal synaptic function of TDP-43 is closely related to NMJ disruption in ALS, and it may exert its effects by influencing molecular mechanisms within motor neurons, skeletal muscles, and glial cells.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Neurosciences
Maize C. Cao, Brigid Ryan, Jane Wu, Maurice A. Curtis, Richard L. M. Faull, Mike Dragunow, Emma L. Scotter
Summary: TDP-43 dysfunction is a molecular characteristic of ALS and FTD. It leads to the loss of normal nuclear function, resulting in impaired RNA regulation and the emergence of cryptic exons. Cryptic exons and differential exon usage are promising markers of TDP-43 dysfunction in ALS/FTD and provide insights into neurodegenerative pathways.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Molly E. V. Swanson, Miran Mrkela, Helen C. C. Murray, Maize C. C. Cao, Clinton Turner, Maurice A. A. Curtis, Richard L. M. Faull, Adam K. K. Walker, Emma L. L. Scotter
Summary: The activation of microglia in ALS is associated with TDP-43 aggregation, with phagocytic state in early-stage disease and dysfunctional state in end-stage disease. These findings enhance our understanding of microglial phenotypes and function in ALS.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Clinical Neurology
Fumiaki Mori, Hina Yasui, Yasuo Miki, Tomoya Kon, Akira Arai, Hidekachi Kurotaki, Masahiko Tomiyama, Koichi Wakabayashi
Summary: This study found that TDP-43 and SGs colocalize at the early stage of TDP-43 aggregation, suggesting the involvement of SGs in the formation of TDP-43 inclusions.
Article
Biochemistry & Molecular Biology
Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco, Edoardo Milanetti
Summary: This article investigates the protein aggregation process in ALS, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. The study proposes and assesses possible association mechanisms between CTFs, and performs molecular docking and additional MD simulations to propose possible complexes and evaluate their stability, focusing on high shape complementarity and involvement of beta 3 and beta 5 strands at the interfaces.
Article
Cell Biology
Saebom Lee, Hye Guk Ryu, Sin Ho Kweon, Hyerynn Kim, Hyeonwoo Park, Kyung-Ha Lee, Sang-Min Jang, Chan Hyun Na, Sangjune Kim, Han Seok Ko
Summary: Non-receptor tyrosine kinase c-Abl is involved in the development of various neurodegenerative disorders. This study reveals that TDP-43 is a novel substrate for c-Abl and its phosphorylation by c-Abl leads to increased levels of TDP-43 in the cytoplasm and the formation of stress granules. In addition, phosphorylation of TDP-43 by c-Abl promotes its aggregation and neuronal cell death.
Article
Immunology
Swetha Ramachandran, Veselin Grozdanov, Bianca Leins, Katharina Kandler, Simon Witzel, Medhanie Mulaw, Albert C. Ludolph, Jochen H. Weishaupt, Karin M. Danzer
Summary: This study found that the activation of T cells is increased in patients with ALS, but the antigen that leads to their activation has not been identified. The study also found that ALS patients have lower levels of T cell activation to TDP-43 and control stimuli compared to healthy individuals.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Donya Pakravan, Emiel Michiels, Anna Bratek-Skicki, Mathias De Decker, Joris Van Lindt, David Alsteens, Sylvie Derclaye, Philip Van Damme, Joost Schymkowitz, Frederic Rousseau, Peter Tompa, Ludo van den Bosch
Summary: This study investigated how phase separation affects the aggregation of TDP-43 protein, finding that liquid-liquid phase separation (LLPS) promotes spontaneous aggregation but hinders seeded aggregation. Analysis of various conditions using buffers showed that stabilizing hydrophobic interactions are more important than destabilizing electrostatic forces. RNA was found to affect the cooperativity between LLPS and aggregation in a reentrant manner.
Article
Neurosciences
Minggang Fang, Sara K. Deibler, Alissa L. Nana, Sarat C. Vatsavayai, Shahid Banday, You Zhou, Sandra Almeida, Alexandra Weiss, Robert H. Brown, William W. Seeley, Fen-Biao Gao, Michael R. Green
Summary: Loss of nuclear TDP-43 function contributes to increased DNA damage in ALS and FTD patients due to defects in DNA repair pathways.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Medicine, General & Internal
Penelope Pfeiffer, Joan R. Coates, Yajaira M. Esqueda, Andrew Kennedy, Kyleigh Getchell, Myra McLenon, Edina Kosa, Abdulbaki Agbas
Summary: Serum-derived exosomes have the potential to serve as surrogate biomarkers for neurodegenerative diseases. Canine degenerative myelopathy can be used as an animal model to study human amyotrophic lateral sclerosis.
ANNALS OF MEDICINE
(2023)