Article
Neurosciences
Argyro Thalia Delizannis, Annelies Nonneman, Wangchen Tsering, An De Bondt, Ilse Van den Wyngaert, Bin Zhang, Emily Meymand, Modupe F. Olufemi, Pyry Koivula, Shaniya Maimaiti, John Q. Trojanowski, Virginia M-Y Lee, Kurt R. Brunden
Summary: The study highlights the complex interplay between microglia, tau pathology, and A beta plaques in the context of Alzheimer's disease. It suggests that microglial function and gene expression, particularly related to TREM2, play crucial roles in the progression of the disease. The findings indicate that targeting microglial depletion and gene variations may offer new therapeutic strategies for AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Longfei Li, Jin Miao, Dandan Chu, Nana Jin, Yunn Chyn Tung, Chun-Ling Dai, Wen Hu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Summary: Findings from this study suggest that the monoclonal tau antibody 77G7 effectively suppresses the seeding activity of AD O-tau and could potentially be developed as an immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Review
Biochemistry & Molecular Biology
Huiqin Zhang, Wei Wei, Ming Zhao, Lina Ma, Xuefan Jiang, Hui Pei, Yu Cao, Hao Li
Summary: Extracellular neuritic plaques and intracellular neurofibrillary tangles, composed of amyloid-beta and phosphorylated tau protein respectively, are hallmark proteins of Alzheimer's disease. The interactions between these proteins have been extensively studied, with A beta accelerating tau phosphorylation, tau mediating A beta toxicity, and potential synergistic effects on microglial cells and astrocytes. Understanding these interactions may lead to new interventions against Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Immunology
Zhi-Xiu Lin, Wen Yang, Qing-Qing Xu, Qiuju Yuan, Yan-Fang Xian
Summary: This study aimed to evaluate the cognitive deficits improving effects of SF on TgCRND8 mice and elucidate the underlying molecular mechanisms. The results showed that SF significantly ameliorated the cognitive deficits in TgCRND8 mice and protected primary mouse neurons against A beta 1-42 induced neurotoxicity. SF is a potent CDK5 inhibitor and a potential therapeutic agent for treatment and prevention of AD.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Neurosciences
Olivia A. Shipton, Clara S. Tang, Ole Paulsen, Mariana Vargas-Caballero
Summary: The study shows that both A beta and tau protein play a role in the development of Alzheimer's disease. A beta affects synaptic deficits in wild-type mice, but not in mice without tau protein. Additionally, CA3-CA1 synapses in the hippocampus with presynaptic axons from the left CA3 are more vulnerable to A beta.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Shuai Zhao, Ziqi Fan, Xinyi Zhang, Zheyu Li, Ting Shen, Kaicheng Li, Yaping Yan, Yunfeng Yuan, Jiali Pu, Jun Tian, Zhirong Liu, Yanxing Chen, Baorong Zhang
Summary: This study found that metformin can inhibit the propagation of tau protein in Alzheimer's disease and reduce its hyperphosphorylation. It also improves learning and memory deficits, suggesting that metformin could be a promising drug for the prevention and early treatment of AD.
Article
Geriatrics & Gerontology
Fei Liu, Ruozhen Wu, Nana Jin, Dandan Chu, Jianlan Gu, Yunn Chyn Tung, Zhihao Hu, Cheng-Xin Gong, Khalid Iqbal
Summary: Two simple assays, capture assay and seeded-tau aggregation assay, were developed to assess tau seeding activity. These assays were proven to be specific and sensitive and can be carried out in a regular biomedical laboratory setting.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Clinical Neurology
Duygu Tosun, Pamela Thropp, Sudeepti Southekal, Bruce Spottiswoode, Rachid Fahmi
Summary: This study used an unsupervised data-driven whole-brain pattern analysis to identify distinct tau accumulation profiles and build baseline models predictive of tau-accumulation type. Screening for fast tau accumulation and A beta positivity in early Alzheimer's disease requires a lower sample size to achieve 80% power for a specific treatment.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Biao Luo, Jian Chen, Gui-Feng Zhou, Xiao-Yong Xie, Jing Tang, Qi-Xin Wen, Li Song, Shi-Qi Xie, Yan Long, Guo-Jun Chen, Xiao-Tong Hu
Summary: Apicidin improves AD symptoms in APP/PS1 mice by regulating the expression of ADAM10, leading to a decrease in A beta levels rather than phosphorylation of tau.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Christine Rother, Ruth E. Uhlmann, Stephan A. Mueller, Juliane Schelle, Angelos Skodras, Ulrike Obermuller, Lisa M. Hasler, Marius Lambert, Frank Baumann, Ying Xu, Carina Bergmann, Giulia Salvadori, Maarten Loos, Irena Brzak, Derya Shimshek, Ulf Neumann, Lary C. Walker, Stephanie A. Schultz, Jasmeer P. Chhatwal, Stephan A. Kaeser, Stefan F. Lichtenthaler, Matthias Staufenbiel, Mathias Jucker
Summary: This study reveals a temporal dissociation between brain Aβ deposition and neurodegeneration, providing new insights into the pathogenesis of Alzheimer's disease.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Bing Zhu, Yan Liu, Spring Hwang, Kailey Archuleta, Huijie Huang, Alex Campos, Rabi Murad, Juan Pina-Crespo, Huaxi Xu, Timothy Y. Huang
Summary: This study found that Trem2 deletion can enhance the spreading of tau in the brain of mice, leading to impaired synaptic function and memory. Furthermore, Trem2 deletion can strengthen the ability of microglia to transmit tau through exosomal vesicles.
MOLECULAR NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Sivaprakasam R. Saroja, Kirill Gorbachev, T. C. W. Julia, Alison M. Goate, Ana C. Pereira
Summary: A protein called glypican-4 (GPC-4) secreted by astrocytes is shown to drive tau hyperphosphorylation induced by APOE4, a genetic risk factor for Alzheimer's disease. This discovery provides insights into the mechanisms underlying tauopathies and highlights the role of GPC-4 in tau accumulation and propagation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna M. Grochowska, Guilherme M. Gomes, Rajeev Raman, Rahul Kaushik, Liudmila Sosulina, Hiroshi Kaneko, Anja M. Oelschlegel, PingAn Yuanxiang, Irene Reyes-Resina, Gonca Bayraktar, Sebastian Samer, Christina Spilker, Marcel S. Woo, Markus Morawski, Juergen Goldschmidt, Manuel A. Friese, Steffen Rossner, Gemma Navarro, Stefan Remy, Carsten Reissner, Anna Karpova, Michael R. Kreutz
Summary: Soluble beta-amyloid peptide (A beta) causes synaptic dysfunction in early-stage Alzheimer's disease (AD) by suppressing the transcriptional activity of CREB. A beta induces nucleocytoplasmic trafficking of Jacob, which leads to transcriptional inactivation of CREB and loss of synapses. The compound Nitarsone restores CREB activity by hindering the assembly of a Jacob/LMO4/PP1 signalosome, preventing synaptic impairment and cognitive decline in mouse models of AD.
Article
Neurosciences
Hee-Jeong Choi, Jin-Hee Park, Yoo Joo Jeong, Jeong-Woo Hwang, Soojung Lee, Heeyong Lee, Eunyoung Seol, Ik-whi Kim, Byung-Yoon Cha, Jinsoo Seo, Minho Moon, Hyang-Sook Hoe
Summary: The study found that intraperitoneal injection of donepezil can reduce the number of Aβ plaques in the brain and decrease glial cell activation in 5xFAD mice. However, it has little effect on tau pathology.
Article
Chemistry, Multidisciplinary
Dong Gil You, Jae Yoon An, Wooram Um, Jae Min Jung, Byeong Hoon Oh, Van Quy Nguyen, Jueun Jeon, Jungmi Lee, Dong-Gyu Jo, Yong Woo Cho, Jae Hyung Park
Summary: Hyaluronic acid-based hydrogels have the potential to reduce wrinkles, while stem cell-derived extracellular vesicles can improve the dermal microenvironment, prolong collagen generation, and serve as a potential antiaging filler for reprogramming the dermis environment.
Article
Biochemistry & Molecular Biology
Yiran Liu, David Castano, Francesco Girolamo, Laia Trigueros-Motos, Han-Gyu Bae, Suat Peng Neo, Jeongah Oh, Pradeep Narayanaswamy, Federico Torta, Kerry Anne Rye, Dong-Gyu Jo, Jayantha Gunaratne, Sangyong Jung, Daniela Virgintino, Roshni R. Singaraja
Summary: The lack of ABCA8 protein disrupts cerebellar myelination and affects the function of oligodendrocyte precursor cells and mature oligodendrocytes, leading to impaired cerebellar conduction velocity and locomotion.
JOURNAL OF LIPID RESEARCH
(2022)
Review
Neurosciences
Luting Poh, Wei Liang Sim, Dong-Gyu Jo, Quynh Nhu Dinh, Grant R. Drummond, Christopher G. Sobey, Christopher Li-Hsian Chen, Mitchell K. P. Lai, David Y. Fann, Thiruma V. Arumugam
Summary: This review aims to provide a comprehensive insight into the molecular and cellular mechanisms involved in the pathogenesis of chronic cerebral hypoperfusion-induced inflammasome signaling in vascular cognitive impairment (VCI).
MOLECULAR NEURODEGENERATION
(2022)
Article
Biochemistry & Molecular Biology
Joo-Yun Byun, Kun Huang, Jong Suk Lee, Wenjie Huang, Li Hu, Xuyu Zheng, Xin Tang, Fengzeng Li, Dong-Gyu Jo, Xinmao Song, Chuang Huang
Summary: Poor prognosis of head and neck squamous cell carcinomas (HNSCCs) is mainly due to resistance to chemotherapy and radiotherapy. Activation of HIF-1 alpha in CD44(+) HNSCC patients was associated with worse prognosis. HIF-1 alpha promoted stemness, resistance, and epithelial-mesenchymal transition in HNSCC CD44(+) cells.
Article
Cell Biology
Jacob K. Sterling, Tae-In Kam, Samyuktha Guttha, Hyejin Park, Bailey Baumann, Amir A.Mehrabani-Tabari, Hannah Schultz, Brandon Anderson, Ahab Alnemri, Shih-Ching Chou, Juan C. Troncoso, Valina L. Dawson, Ted M. Dawson, Joshua L. Dunaief
Summary: The aggregation and accumulation of a-synuclein drive neurodegeneration in Parkinson's disease (PD). Microglia activated by misfolded a-synuclein release interleukin 6 (IL-6), which induces changes in neuronal iron transcriptome and leads to cellular iron accumulation. The IL-6-mediated cellular iron sequestration response (CISR) contributes to synuclein-induced neurodegeneration in PD patients.
Article
Cell Biology
Hark Kyun Kim, Junhyung Cho, Eunae Kim, Junsik Kim, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Younmin Shin, Leon F. Palomera, Jinsu Park, Seung Hyun Baek, Han-Gyu Bae, Yoonsuk Cho, Jihoon Han, Jae Hoon Sul, Jeongmi Lee, Jae Hyung Park, Yong Woo Cho, Wonsik Lee, Dong-Gyu Jo
Summary: This study presents a method of using small extracellular vesicles (sEVs) to deliver soluble ACE2 (sACE2) and inhibit the entry of SARS-CoV-2. The researchers found that sACE2 variants loaded in sEVs showed higher antiviral efficacy compared to wild-type sACE2, and could inhibit the entry of different variants of SARS-CoV-2.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Article
Geriatrics & Gerontology
Gavin Yong-Quan Ng, Dominic Paul Lee Kok Sheng, Han-Gyu Bae, Sung Wook Kang, David Yang-Wei Fann, Jinsu Park, Joonki Kim, Asfa Alli-Shaik, Jeongmi Lee, Eunae Kim, Sunyoung Park, Jeung-Whan Han, Vardan Karamyan, Eitan Okun, Thameem Dheen, Manoor Prakash Hande, Raghu Vemuganti, Karthik Mallilankaraman, Lina H. K. Lim, Brian K. Kennedy, Grant R. Drummond, Christopher G. Sobey, Jayantha Gunaratne, Mark P. Mattson, Roger Sik-Yin Foo, Dong-Gyu Jo, Thiruma V. Arumugam
Summary: Intermittent fasting can modulate H3K9 trimethylation in the cerebellum and trigger transcriptomic changes associated with metabolic processes. Part of the epigenomic and transcriptomic modulations induced by IF can be preserved for at least 3 months post-IF, but termination of IF results in a loss of H3K9 trimethylation regulation of the transcriptome.
Review
Pharmacology & Pharmacy
Yoonsuk Cho, Han-Gyu Bae, Eitan Okun, Thiruma V. Arumugam, Dong-Gyu Jo
Summary: APP is an evolutionarily conserved transmembrane protein that serves as a precursor to amyloid-beta peptides, which are implicated in Alzheimer's disease. Studies have shown diverse pathological and physiological functions of APP and its cleavage products, but their roles are not fully understood. Current research focuses on APP processing and potential therapeutic approaches for Alzheimer's disease.
PHARMACOLOGY & THERAPEUTICS
(2022)
Correction
Pharmacology & Pharmacy
Yoonsuk Cho, Han-Gyu Bae, Eitan Okun, Thiruma V. Arumugam, Dong-Gyu Jo
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Jiyeon Seo, Hongik Hwang, Heesung Sohn, Eunsil Cho, Sunmin Jung, Soohyun Kim, Seung Min Um, Ji Yeon Kim, Muwon Kang, Yuri Choi, Jong-Hwan Kim, Mirang Kim, Seon-Young Kim, Sun-Kyung Lee, Joohong Ahnn, Hyewhon Rhim, Dong-Gyu Jo, Eunjoon Kim, Mikyoung Park
Summary: Spatial learning and memory flexibility are regulated by long-term potentiation (LTP) and long-term depression (LTD) at the cellular level. This study demonstrates that Ccny knockout (KO) mice exhibit enhanced LTP, weak LTD, and improved spatial learning and memory. CCNY modulates memory flexibility by modulating the cofilin-actin signaling pathway in the hippocampus.
MOLECULAR PSYCHIATRY
(2023)
Article
Cell Biology
Seo-Hyun Kim, Young-Sin Cho, Youbin Kim, Jisu Park, Seung-Min Yoo, Jimin Gwak, Youngwon Kim, Youngdae Gwon, Tae-in Kam, Yong-Keun Jung
Summary: Impaired endolysosomal integrity plays a crucial role in the development of Alzheimer's disease (AD). The vacuolar ATPase (V-ATPase) complex acts as a proteotoxic receptor that binds to amyloid beta (Aβ) and hyperphosphorylated MAPT/Tau (p-MAPT/Tau), leading to endolysosomal dysfunction and subsequent neurodegeneration. The identification of HYAL as a suppressor of endolysosomal dysfunction provides potential therapeutic targets for AD treatment. Additionally, the interaction between hyaluronic acid (HA) and its receptor CD44 may alleviate neurotoxicity in affected neurons via V-ATPase.
Review
Geriatrics & Gerontology
Jeongyeon Nam, Youngdae Gwon
Summary: Biomolecular condensates are subcellular organizations that assemble functionally related proteins and nucleic acids through liquid-liquid phase separation. They are susceptible to disruptions and are implicated in the pathogenesis of neurodegenerative diseases. The pathological transition of biomolecular condensates can promote protein aggregation, and specific protein or protein-RNA complexes in neurons display liquid-like properties. Understanding the role of neuronal biomolecular condensates is important for researching neurodegeneration.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Vismitha Rajeev, David Y. Fann, Quynh Nhu Dinh, Hyun Ah Kim, T. Michael De Silva, Dong-Gyu Jo, Grant R. Drummond, Christopher G. Sobey, Mitchell K. P. Lai, Christopher Li-Hsian Chen, Thiruma V. Arumugam
Summary: Chronic cerebral hypoperfusion (CCH) is an important mechanism in vascular cognitive impairment (VCI). Intermittent fasting (IF) has neuroprotective effects against CCH-induced neurovascular pathologies by reducing leaky microvessels, blood-brain barrier breakdown, and loss of tight junctional proteins.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Seo-Hyuk Chang, Jaeyool Jang, Seungjun Oh, Jung-Hoon Yoon, Dong-Gyu Jo, Ui Jeong Yun, Kye Won Park
Summary: Research demonstrates that stimulation of beta 3-adrenergic receptors (beta 3-AR) in adipocytes can increase the expression of Ucp1 and Hmox1, indicating a functional interaction between Nrf2 and beta 3-AR signaling. Nrf2 directly activates the Ucp1 promoter and inhibiting Nrf2 results in decreased expression of Ucp1 and Hmox1.