Article
Cell Biology
Christopher Beneduce, Stephanie Nguyen, Nathaniel Washburn, John Schaeck, Robin Meccariello, Kimberly Holte, Daniel Ortiz, Anthony M. Manning, Carlos J. Bosques, Elma Kurtagic
Summary: Fc glycosylation is crucial for antibody activity, and Fc sialylation is important for anti-inflammatory effects of IgGs. However, in vitro models using monomeric forms of antibodies have limited ability to determine the structure-activity relationship of Fc glycosylation. To overcome this, we utilized Fc-containing molecules displayed in monovalent and multivalent forms, and found that sialic acid mediates the phosphorylation of Fc?RIIb when IgG-Fc is displayed in a multivalent manner. This study provides new insights into the impact of Fc sialylation on immune cell signaling and characterization of anti-inflammatory activity of Fc-containing therapeutics.
Article
Biochemistry & Molecular Biology
Dieter Petit, Manuel Hitzenberger, Matthias Koch, Sam Lismont, Katarzyna Marta Zoltowska, Thomas Enzlein, Carsten Hopf, Martin Zacharias, Lucia Chavez-Gutierrez
Summary: This study investigates the interactions between an imidazole-based GSM and its target gamma-secretase-APP, and reveals that a part of the modulator interacts with a binding site on gamma-secretase, triggering rearrangements and stabilizing enzyme-substrate interactions.
Article
Immunology
Shady Estfanous, Kylene P. Daily, Mostafa Eltobgy, Nicholas P. Deems, Midhun N. K. Anne, Kathrin Krause, Asmaa Badr, Kaitlin Hamilton, Cierra Carafice, Ahmad Hegazi, Arwa Abu Khweek, Hesham Kelani, Shahid Nimjee, Hamdy Awad, Xiaoli Zhang, Estelle Cormet-Boyaka, Hesham Haffez, Sameh Soror, Adel Mikhail, Gerard Nuovo, Ruth M. Barrientos, Mikhail A. Gavrilin, Amal O. Amer
Summary: The study revealed that autophagy function in microglia is impaired in Alzheimer's Disease (AD), with elevated levels of miR-17 potentially leading to decreased NBR1 expression and affecting A beta degradation. Inhibiting miR-17 can improve autophagy function in AD microglia, offering a potential mechanism for therapeutic interventions in AD patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Bruno P. Imbimbo, Stefania Ippati, Mark Watling, Camillo Imbimbo
Summary: According to the beta-amyloid (A beta) hypothesis, brain A beta accumulation is the primary cause of cognitive deficit and dementia in Alzheimer's disease (AD). While many anti-A beta drugs have failed in clinical trials, recent studies have shown encouraging results for antibodies that clear amyloid plaques. These findings suggest that decreased levels of soluble monomeric A beta may be the main driver of AD, rather than the aggregated forms.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Chemistry, Medicinal
Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Summary: Alzheimer's disease (AD) is a difficult to treat progressive neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) plaques in the brain. A beta interacts with various receptors on the plasma membrane and mediates signaling pathways that contribute to the development of AD. Despite ongoing research, there are currently no effective medications for AD. This review discusses the importance of A beta in the pathogenesis of AD, recent progress in targeting A beta-related receptors and compounds, and the challenges and opportunities in developing effective therapies for AD.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Cell Biology
Akshay Kapadia, Sandra Theil, Sabine Opitz, Nadia Villacampa, Hannes Beckert, Susanne Schoch, Michael. T. Heneka, Sathish Kumar, Jochen Walter
Summary: This study assessed the effect of Aβ phosphorylation on neuronal autophagy and the endo-lysosomal pathway. It found that the phosphorylation state of Aβ impacts its uptake, sorting, and effects on neuronal autophagy and lysosomal function.
Article
Cell Biology
Magdalena Antonino, Paula Marmo, Carlos Leandro Freites, Gonzalo Emiliano Quassollo, Maria Florencia Sanchez, Alfredo Lorenzo, Elena Anahi Bignante
Summary: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) in the brain, which is produced by the cleavage of amyloid precursor protein (APP). Aβ assemblies enhance the interaction between APP and BACE1, leading to increased production and accumulation of Aβ. This process involves Aβ-APP/Go signaling and Gβγ subunit signaling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Zhiwu Dong, Hongjun Gu, Qiang Guo, Xianglu Liu, Feifei Li, Huiling Liu, Li Sun, Huimin Ma, Kewen Zhao
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of beta-amyloid (Aβ) in the brain. This study found that the level of miR-342-5p was decreased in circulating small extracellular vesicles from Alzheimer's disease patients compared to healthy controls, and miR-342-5p played a role in Aβ formation by modulating BACE1 expression.
Article
Biochemistry & Molecular Biology
Ryota Suzuki, Haruka Takahashi, Chika Yoshida, Masafumi Hidaka, Tomohisa Ogawa, Eugene Futai
Summary: In this study, the APP mutation T714I, which is associated with familial Alzheimer's disease, was found to severely reduce the cleavage of A beta. Secondary mutations were identified that restored the cleavage of APP T714I and could modulate the production of A beta species in mammalian cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Jiaying Hu, Leyan Zheng, Ziyu Guan, Kexin Zhong, Fankai Huang, Qiankai Huang, Jing Yang, Weiyun Li, Shanshan Li
Summary: This article reviews the generation and clearance pathways of A8, aberrant gamma oscillation in AD, and the therapeutic effect of sensory gamma entrainment on AD, and discusses these results based on stimulus parameters and possible potential mechanisms. This provides support for sensory gamma entrainment targeting A8 to improve AD.
BRAIN RESEARCH BULLETIN
(2023)
Article
Virology
Hailong Li, Kristen A. McLaurin, Charles F. Mactutus, Benjamin Likins, Wenfei Huang, Sulie L. Chang, Rosemarie M. Booze
Summary: The prevalence of HIV-1 associated neurocognitive disorders (HAND) is higher in older individuals, and using HIV-1 Tg rats as a model, researchers found abnormal beta-amyloid accumulation in the prefrontal cortex and hippocampus, suggesting a potential mechanism underlying synaptodendritic damage in HAND.
Review
Biochemistry & Molecular Biology
Anne-Cathrine S. Vogt, Gary T. Jennings, Mona O. Mohsen, Monique Vogel, Martin F. Bachmann
Summary: Alzheimer's disease is the most common form of dementia and is responsible for 60-70% of cases. The number of people with dementia is expected to triple by 2050 due to an aging population. Currently, there are only symptomatic treatments available, making it crucial to develop novel therapeutic strategies to prevent or delay the onset of Alzheimer's disease. This mini-review focuses on the understanding of Alzheimer's disease pathobiology and discusses current immunomodulating therapies targeting amyloid-beta protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hikari Watanabe, Chika Yoshida, Masafumi Hidaka, Tomohisa Ogawa, Taisuke Tomita, Eugene Futai
Summary: Through studying Aph1 mutations and using a yeast gamma-secretase assay, we found that the L30F/T164A mutation can activate gamma-secretase activity, leading to increased production of Aβ in mouse embryonic fibroblasts without apparent modulatory function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hrishita Das, Sukanya Sarkar, Ramesh K. Paidi, Subhas C. Biswas
Summary: Accumulation of amyloid-beta in the brain is a major trigger for Alzheimer's disease pathogenesis. Mild DNA damage leads to increased production of Aβ. Mitochondrial fusion and the protein MFN2 play a role in this process, potentially as an adaptive response to ER stress, which may contribute to increased Aβ production.
Review
Neurosciences
Gunnar Nordvall, Johan Lundkvist, Johan Sandin
Summary: Recent clinical data have shown that removing A beta-amyloid plaques in early Alzheimer's disease can slow down disease progression. This progress validates the amyloid cascade hypothesis and highlights the importance of targeting A beta-amyloid for therapeutic purposes. It also suggests that reducing the production of amyloidogenic A beta can prevent the formation of A beta-pathology. Further research is needed to explore the potential of gamma-secretase modulators in preventing and treating Alzheimer's disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Sang-Ha Baik, Sharmelee Selvaraji, David Y. Fann, Luting Poh, Dong-Gyu Jo, Deron R. Herr, Shenpeng R. Zhang, Hyun Ah Kim, Michael De Silva, Mitchell K. P. Lai, Christopher Li-Hsian Chen, Grant R. Drummond, Kah-Leong Lim, Christopher G. Sobey, Thiruma Arumugam
Summary: This study investigated the hippocampal gene expression profile of young and old mice subjected to cerebral hypoperfusion, revealing common cellular signaling pathways likely important in the pathophysiology of vascular dementia. While there were similarities in the effects of BCAS and aging, the changes in hippocampal gene expression differed between young and old mice. Over 30 days, BCAS had minimal effect on cerebral blood flow or hippocampal gene expression in aged mice, suggesting age-related differences in response to hypoperfusion.
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)