Alzheimer's disease (AD) is the most common cause of dementia, with the accumulation of amyloid beta peptide (Aβ) being one of the main causes of the disease. Fragile X mental retardation protein (FMRP), encoded by fragile X mental retardation 1 (Fmr1), is an RNA-binding protein that represses translation of its bound mRNAs or exerts other indirect mechanisms that result in translational suppression. Because the accumulation of Aβ has been shown to cause translational suppression resulting from the elevated cellular stress response, in this study we asked whether and how Fmr1 is involved in Aβ-induced translational regulation. Our data first showed that the application of synthetic Aβ peptide induces the expression of Fmr1 in cultured primary neurons. We followed by showing that Fmr1 is required for Aβ-induced translational suppression, hyposynchrony of neuronal firing activity, and loss of excitatory synapses. Mechanistically, we revealed that Fmr1 functions to repress the expression of phosphatases including protein phosphatase 2A (PP2A) and protein phosphatase 1 (PP1), leading to elevated phosphorylation of eukaryotic initiation factor 2-α (eIF2α) and eukaryotic elongation factor 2 (eEF2), and subsequent translational suppression. Finally, our data suggest that such translational suppression is critical to Aβ-induced hyposynchrony of firing activity, but not the loss of synapses. Altogether, our study uncovers a novel mechanism by which Aβ triggers translational suppression and we reveal the participation of Fmr1 in altered neural plasticity associated with Aβ pathology. Our study may also provide information for a better understanding of Aβ-induced cellular stress responses in AD.
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http://dx.doi.org/10.1002/jcp.30754 | DOI Listing |
RMD Open
January 2025
Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.
Objective: To delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes.
Methods: RA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation.
J Ethnopharmacol
January 2025
Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address:
Ethnopharmacological Relevance: Xinbao pill (XBP) is a renowned Chinese patent medicine, primarily efficacious in warming and nourishing the heart and kidneys, supplementing Qi to boost Yang, and promoting blood circulation to remove blood stasis. XBP has been utilized for the treatment of chronic heart failure (CHF) for nearly 30 years, but the lack of clarity regarding the active ingredients of XBP against CHF has hindered its clinical application and further promotion.
Aim Of The Study: To comprehensively elucidate the efficacy-specific ingredients and potential mechanism of XBP against CHF.
Cell Biosci
January 2025
Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Background: Myelin-laden foamy macrophages accumulate extensively in the lesion epicenter, exhibiting characteristics of autophagolysosomal dysfunction, which leads to prolonged inflammatory responses after spinal cord injury (SCI). Trehalose, known for its neuroprotective properties as an autophagy inducer, has yet to be fully explored for its potential to mitigate foamy macrophage formation and exert therapeutic effects in the context of SCI.
Results: We observed that trehalose significantly enhances macrophage phagocytosis and clearance of myelin in a dose-dependent manner in vitro.
J Nanobiotechnology
January 2025
Department of Interventional Radiology, Key Laboratory of Interventional Radiology of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, China.
Excessive vascularization during tracheal in-stent restenosis (TISR) is a significant but frequently overlooked issue. We developed an anti-inflammatory coupled anti-angiogenic airway stent (PAGL) incorporating anlotinib hydrochloride and silver nanoparticles using advanced electrospinning technology. PAGL exhibited hydrophobic surface properties, exceptional mechanical strength, and appropriate drug-release kinetics.
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January 2025
The First People's Hospital of Lin'an District, No. 360, Yikang Street, Jinnan Subdistrict, Lin'an District, Hangzhou, Zhejiang, 311300, China.
Background: Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.
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