Article
Multidisciplinary Sciences
Yuechuan Xu, Kaitlin Knapp, Kyle N. Le, Nicholas P. Schafer, Mohammad S. Safari, Aram Davtyan, Peter G. Wolynes, Peter G. Vekilov
Summary: The research delves into the molecular pathways of amyloid fibrillization, revealing the presence of a complex at the fibril tip supported by nonnative contacts that hinder fibril growth. It also uncovers the dynamics of coupled structuring and assembly during fibril growth, which are more intricate than during the folding of most globular proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Ketaki D. Belsare, Haifan Wu, Dibyendu Mondal, Annalise Bond, Erika Castillo, Jia Jin, Hyunil Jo, Addison E. Roush, Kala Bharath Pilla, Andrej Sali, Carlo Condello, William F. DeGrado
Summary: The soluble form of TREM2, sTREM2, was found to bind to fibrillar A1340 and A1342, enhancing their uptake into cells. sTREM2 inhibited the secondary nucleation step in A13 fibrillization, but had little effect on the primary nucleation pathway. The disease-associated mutant R47H showed reduced uptake and functional responses to fibrils. Molecular modeling revealed the binding mode of sTREM2 to A13 fibrils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Arenn F. F. Carlos, Nirubol Tosakulwong, Stephen D. D. Weigand, Matthew L. L. Senjem, Christopher G. G. Schwarz, David S. S. Knopman, Bradley F. F. Boeve, Ronald C. C. Petersen, Aivi T. T. Nguyen, R. Ross Reichard, Dennis W. W. Dickson, Clifford R. R. Jack Jr, Val Lowe, Jennifer L. L. Whitwell, Keith A. A. Josephs
Summary: This study investigated the impact of age and TDP-43 pathology on the volume-uptake mismatch in older Alzheimer's disease patients. The results showed that TDP-43 pathology was associated with reduced medial temporal volumes but not with F-18-flortaucipir uptake. The effect size of TDP-43 pathology remained consistent across the age spectrum, but in older age, the mean volumes moved towards those of TDP-43-positive cases, reflecting the increasing frequency of TDP-43 pathology with age.
ALZHEIMERS & DEMENTIA
(2022)
Review
Neurosciences
Axel Meneses, Shunsuke Koga, Justin O'Leary, Dennis W. Dickson, Guojun Bu, Na Zhao
Summary: TDP-43, a protein encoded by the TARDBP gene, plays a crucial role in various neurodegenerative diseases such as ALS, FTLD, and AD. Its pathology is associated with cognitive impairment severity and genetic risk factors, such as APOE4, in AD.
MOLECULAR NEURODEGENERATION
(2021)
Article
Biochemistry & Molecular Biology
Yu Zhang, Yuying Liu, Wenhui Zhao, Yunxiang Sun
Summary: The study demonstrates that SWCNT-OH has excellent anti-amyloid properties, inhibiting the fibrillization of beta 2m(21)(-)(31) peptides and destroying pre-formed proto-fibrils.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Neurosciences
Loreto Martinez-Gonzalez, Eva P. Cuevas, Carlota Tosat-Bitrian, Vanesa Nozal, Carmen Gil, Valle Palomo, Angeles Martin-Requero, Ana Martinez
Summary: Recent research has shown that abnormal TDP-43 protein aggregation in Alzheimer's disease patients may play a significant role in the pathology of the disease. This study investigated the use of TTBK1 and CK1 inhibitors to target TDP-43 pathology in AD patients. The results demonstrate that these inhibitors can reduce TDP-43 phosphorylation and prevent cell-to-cell propagation of the disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Caitlin S. Latimer, Jade G. Stair, Joshua C. Hincks, Heather N. Currey, Thomas D. Bird, C. Dirk Keene, Brian C. Kraemer, Nicole F. Liachko
Summary: In addition to amyloid beta and tau, TDP-43 also plays a role in the pathology of Alzheimer's disease. TDP-43 enhances the neurotoxicity of tau, leading to cognitive decline and neurodegeneration. Studying this protein co-morbidity is crucial for understanding and treating mixed pathology Alzheimer's disease.
DISEASE MODELS & MECHANISMS
(2022)
Article
Multidisciplinary Sciences
Yanjun Zhou, Nanqu Huang, Yuanyuan Li, Zhisheng Ba, Yong Luo
Summary: This study investigated the protective effect of icaritin (ICT) in SH-SY5Y cells infected with TAR DNA-binding domain protein 43 (TDP-43) and its underlying mechanism by examining the expression of autophagy-related proteins. The results showed that ICT intervention increased cell viability, decreased TDP-43 expression, and reduced the expression of cleaved Caspase-3, Beclin-1, and LC3-II/I, while increasing the expression of p62. This suggests that ICT has a protective effect on TDP-43-induced neuronal cell injury by reducing TDP-43 protein expression and inhibiting autophagy.
Article
Neurosciences
Yuan Tian, Yi Wang, Angela M. Jablonski, Yinghui Hu, Jonathan A. Sugam, Markus Koglin, Shawn J. Stachel, Heather Zhou, Jason M. Uslaner, Sophie Parmentier-Batteur
Summary: Elevated levels of TTBK1 were observed in the motor cortex of ALS patients, and TTBK1 was found to phosphorylate TDP-43 directly, leading to the formation of high molecular species and subsequent neuronal loss. Inhibiting TTBK1 significantly alleviated TDP-43 phosphorylation and aggregation, suggesting a potential therapeutic strategy for ALS and FTLD.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Virginia Estades Ayuso, Sarah Pickles, Tiffany Todd, Mei Yue, Karen Jansen-West, Yuping Song, Jesus Gonzalez Bejarano, Bailey Rawlinson, Michael DeTure, Neill R. Graff-Radford, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, Keith A. Josephs, Leonard Petrucelli, Mercedes Prudencio
Summary: In AD patients with TDP-43 proteinopathy, misspliced cryptic or skiptic RNAs of specific genes have been detected, indicating the involvement of TDP-43 dysfunction in AD pathogenesis. This finding provides a potential new therapeutic and diagnostic target for AD.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biology
Keisuke Takeda, Aoi Uda, Mikihiro Mitsubori, Shun Nagashima, Hiroko Iwasaki, Naoki Ito, Isshin Shiiba, Satoshi Ishido, Masaaki Matsuoka, Ryoko Inatome, Shigeru Yanagi
Summary: The loss of MITOL exacerbates cognitive decline in AD mouse models by promoting the accumulation of Aβ oligomers, rather than Aβ plaques, suggesting that alteration in mitochondrial morphology plays a key role in Alzheimer's disease progression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Jinyoung Park, Yanwei Wu, Wei Shao, Tania F. Gendron, Sophie J. F. van der Spek, Grigorii Sultanakhmetov, Avik Basu, Paula Castellanos Otero, Caroline J. Jones, Karen Jansen-West, Lillian M. Daughrity, Sadhna Phanse, Giulia del Rosso, Jimei Tong, Monica Castanedes-Casey, Lulu Jiang, Jenna Libera, Bjorn Oskarsson, Dennis W. Dickson, David W. Sanders, Clifford P. Brangwynne, Andrew Emili, Benjamin Wolozin, Leonard Petrucelli, Yong-Jie Zhang
Summary: C9orf72 repeat expansions are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly(GR) proteins interact with key proteins involved in stress granule (SG) formation, such as G3BP1 and YTHDF proteins, to promote the formation of toxic cytoplasmic inclusions in neurons, leading to disease progression. Inhibiting the interactions between poly(GR) and these proteins or reducing the levels of poly(GR) may be promising therapeutic strategies for c9FTD/ALS.
Article
Engineering, Chemical
Wei Liu, Xueting Sun, Xiaoyan Dong, Yan Sun
Summary: The chiral influence of peptide inhibitors on Aβ fibrillogenesis and cytotoxicity was investigated in this study. It was found that the D-enantiomer exhibited stronger inhibition effect on Aβ self-assembly compared to the L-enantiomer, with significant differences in their reaction.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2022)
Letter
Clinical Neurology
Mayuko Sakuwa, Tadashi Adachi, Yuki Suzuki, Kentaro Yoshida, Hiroki Fukuda, Hiroshi Miura, Yoshiki Adachi, Ristuko Hanajima
Summary: This study reports the first Japanese autopsy case of Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation with atypical TDP43 proteinopathy, suggesting that TDP43 protein may play an important role in the clinical presentation of individuals carrying the LRRK2 G2019S mutation.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Clinical Neurology
Laura Pasetto, Maurizio Grassano, Silvia Pozzi, Silvia Luotti, Eliana Sammali, Alice Migazzi, Manuela Basso, Giovanni Spagnolli, Emiliano Biasini, Edoardo Micotti, Milica Cerovic, Mirjana Carli, Gianluigi Forloni, Giovanni De Marco, Umberto Manera, Cristina Moglia, Gabriele Mora, Bryan J. Traynor, Adriano Chio, Andrea Calvo, Valentina Bonetto
Summary: Deficiency of PPIA leads to a neurodegenerative disease with features resembling frontotemporal dementia in mice, characterized by mislocalization and aggregation of Ran protein in the brain, affecting the expression levels of TDP-43 and proteins involved in synaptic function. These findings suggest that defective PPIA function causes TDP-43 mislocalization and dysfunction, implicating it as a potential target for future therapeutic approaches.
Article
Neurosciences
Shih-Ling Huang, Lien-Szu Wu, Min Lee, Chin-Wen Chang, Wei-Cheng Cheng, Yu-Sheng Fang, Yun-Ru Chen, Pei-Lin Cheng, Che-Kun James Shen
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Ya-Ling Chiang, Yu-Jen Chang, Yun-Ru Chen, Ing-Shouh Hwang
Summary: The study revealed the impact of nitrogen and oxygen molecules on the morphology of protein fibrils, leading to different aggregation patterns under different gas conditions. The findings contribute to a better understanding of the aggregation mechanism of amyloid fibrils and potential therapeutic applications.
Article
Chemistry, Physical
Kai-Wei Hu, Hsiu-Fang Fan, Han-Chen Lin, Jian-Wei Huang, Yu-Chieh Chen, Cai-Ling Shen, Yao-Hsiang Shih, Ling-Hsien Tu
Summary: The study showed that glycation significantly slows down the aggregation process of A beta and induces more cytotoxicity, especially at position 28. The higher toxicity might result from a relatively stable oligomeric form of the peptide, rather than ROS production.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Analytical
Katrin H. P. Vu, Ming-Che Lee, Gerhard H. Blankenburg, Yu-Jen Chang, Ming-Lee Chu, Andreas Erbe, Leonardo Lesser-Rojas, Yun-Ru Chen, Chia-Fu Chou
Summary: The study introduces a versatile platform using sub-10 nm nanogap electrodes for manipulating and sensing biomolecules in physiological conditions at a low copy number. This platform traps molecules via dielectrophoresis (DEP) across the nanogap, serving as a surface-enhanced Raman spectroscopy hotspot. The platform is demonstrated to be useful in studying the structural differences between A beta 40 and ZnA beta 40 peptides at different aggregation stages in physiologically relevant concentrations and in a solution phase.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ming-Che Lee, Yi-Hung Liao, Shih-Hui Chen, Yun-Ru Chen
Summary: Alzheimer's disease is the most prevalent and devastating neurodegenerative disease in the elderly, characterized by senile plaques composed of amyloid-beta fibrils. Mutations at the E22 position were found to increase the thermal stability and seeding function of Aβ fibrils, as demonstrated in this study.
Article
Biochemistry & Molecular Biology
Ying-Shuang Chang, Chih-Lung Lin, Chu-Wan Lee, Han-Chen Lin, Yi-Ting Wu, Yao-Hsiang Shih
Summary: This study investigates the effect of running exercise on 2K1C-induced hypertension in mice. The results show that running exercise improves spatial memory and neurogenesis impairment, normalizes RAS activity, and reduces blood-brain barrier leakage, indicating its potential in preventing hypertension-induced brain impairment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yuh Shen Lye, Yun-Ru Chen
Summary: This review emphasizes the role of oligomeric TDP-43 in both physiological and pathological conditions and discusses the potential mechanisms of oligomer formation. By studying TDP-43 oligomers, we can gain a better understanding of their involvement in neurodegenerative diseases and provide new therapeutic strategies for these diseases.
Article
Plant Sciences
Wu-Fu Chen, Yao-Hsiang Shih, Hsuan-Chih Liu, Cheng- Cheng, Chi- Chang, Chung-Yi Chen, In-Pin Lin, Mei-Ying Lin, Chien-Hsing Lee
Summary: The study investigated the anti-inflammatory and antioxidant effects of flavonoid 6-methoxyflavone (6-MeOF) in microglia-mediated neuroinflammation. The results demonstrated that 6-MeOF reduced the expression of pro-inflammatory mediators, inhibited the activation of NF-Kappa B and MAPK signaling pathways, decreased the levels of reactive oxygen species (ROS), and induced the expression of antioxidant enzymes. Furthermore, 6-MeOF prevented the proliferation of microglia. These findings suggest that 6-MeOF has the potential to be used as a therapeutic agent for neuroinflammatory disorders.
Article
Multidisciplinary Sciences
Jin-Lin Wu, Tung-Hung Su, Pei-Jer Chen, Yun-Ru Chen
Summary: This study found that A-SAA biomarkers have significant value in detecting early-stage HCC in cirrhotic patients, with the PMCA signal performing even better than AFP.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Yu-Hao Lin, Yao-Hsiang Shih, Ye Vone Yap, Yen-Wei Chen, Hsiang-Lin Kuo, Tsung-Yun Liu, Li-Jin Hsu, Yu-Min Kuo, Nan-Shan Chang
Summary: When WWOX is downregulated in middle age, protein aggregation occurs and lasts for more than 30 years, leading to the development of Alzheimer's disease. Treatment with neurotoxin MPP+ results in the upregulation and aggregation of TPC6A Delta, which is a common initiator for both Alzheimer's disease and Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Bo-Wen Lin, Pao-Yen Lin, Yao-Hsiang Shih, Cheng-Lin Wu, Yeng-Ting Wu, Meei Jyh Jiang
Summary: The study aims to identify the role of turbulent components of blood flow in promoting aortic lumen dilatation. Moderate coarctation of the porcine abdominal aorta was induced to create overt flow turbulence and lead to dilatation. A new metric, fluctuation intensity (FI), was proposed to measure turbulent fluctuations of pulsatile aortic flow. Analysis revealed that high-intensity, high-frequency components of blood flow fluctuations induced by coarctation promote elastic lamella degradation and aortic lumen dilatation. The proposed metric, HFFI, was found to be a useful predictor of post-stenotic dilatation (PSD).
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
(2023)
Article
Nanoscience & Nanotechnology
Yu -Han Su, Han-Chen Lin, Hsing-Yen Li, Chih-Hsuan Lien, Yao-Hsiang Shih, Chian -Hui Lai
Summary: The aim of this study was to develop a carbohydrate silica nanocomposite, M-mDOX@SiO2, which can specifically target cancer cells and release the drug doxorubicin (DOX) specifically in an acidic tumor microenvironment (TME). The synthesized M-mDOX@SiO2 demonstrated high antitumor efficacy, making it a promising drug delivery carrier.
ACS APPLIED NANO MATERIALS
(2023)
Article
Clinical Neurology
Phillip Smethurst, Emmanuel Risse, Giulia E. Tyzack, Jamie S. Mitchell, Doaa M. Taha, Yun-Ru Chen, Jia Newcombe, John Collinge, Katie Sidle, Rickie Patani