Article
Neurosciences
Lauren Owens, Joshua Bracewell, Alexandre Benedetto, Neil Dawson, Christopher Gaffney, Edward Parkin
Summary: In this study, the depletion of sA beta PP alpha and the accumulation of sA beta PP alpha' were found to contribute to cytotoxicity in AD-related neuroblastoma cells overexpressing BACE1. These findings provide new insights into the pathological mechanisms of AD and raise questions about previous studies using 6E10 antibody as a biomarker.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Review
Pharmacology & Pharmacy
Parthasaradhireddy Tanguturi, John M. Streicher
Summary: Alzheimer's disease (AD) is a complex neurological disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Inhibiting the expression and function of BACE1/gamma-secretase, enzymes involved in the amyloidogenic pathway, shows promise in AD therapy. The opioid receptor family, which modulates the etiology of AD progression, could be a potential target for drug development.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Santiago Ramirez, Suelyn Koerich, Natalia Astudillo, Nicole De Gregorio, Rabab Al-Lahham, Tyler Allison, Natalia Pessoa Rocha, Fei Wang, Claudio Soto
Summary: This study aimed to evaluate the effect of removing Aβ from blood plasma on the accumulation of amyloid plaques in the brain. The results showed a reduction in Aβ levels in the plasma and insoluble brain fractions, as well as a decrease in amyloid plaque burden and changes in plaque size distribution in the cortex and hippocampus. These findings support the importance of targeting Aβ in the periphery and suggest plasma exchange as a potential non-pharmacological strategy for slowing down AD pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matthias Koch, Thomas Enzlein, Shu-Yu Chen, Dieter Petit, Sam Lismont, Martin Zacharias, Carsten Hopf, Lucia Chavez-Gutierrez
Summary: This study explores the mechanism that controls the processing of the amyloid precursor protein (APP) by gamma-secretases, which is crucial in determining the length of amyloid-beta (A beta) peptides and their role in Alzheimer's disease (AD) pathogenesis. The researchers found that polar interactions established by the APPC99 ectodomain (ECD) play a key role in regulating the cleavage of APP by gamma-secretases. Increasing the hydrophobicity of APPC99-ECD attenuates substrate-driven product release and rescues the effects of Alzheimer's disease-associated pathogenic gamma-secretase and APP variants on A beta length. Furthermore, the study reveals that APPC99-ECD facilitates the production of longer A beta peptides caused by certain gamma-secretase inhibitors. These findings highlight the importance of the APPC99-ECD in regulating gamma-secretase activity and suggest it as a potential target for developing compounds that can selectively promote APP processing by these enzymes.
Article
Biochemistry & Molecular Biology
Rahim Ullah, Gowhar Ali, Ajmal Khan, Sajjad Ahmad, Ahmed Al-Harrasi
Summary: The study investigated the effects of 3NCP on AD using 5xFAD mouse models, showing potential therapeutic effects in reducing amyloid plaques and improving learning and memory. In vivo studies demonstrated that 3NCP did not induce anxiety, significantly reduced beta-amyloid plaques, and decreased BACE-1 expression in the brain tissues. This suggests that 3NCP may be a promising candidate for future AD treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Jia Miao, Minqian Miao, Yue Jiang, Min Zhao, Qing Li, Yuan Zhang, Yi An, Kanyi Pu, Qingqing Miao
Summary: A NIR-II fluorescent reporter with a donor-pi-acceptor architecture was developed for specific detection of A beta plaques in AD-model mice, enabling non-invasive imaging and deep deciphering of AD progression.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Genetics & Heredity
Alex G. Nackenoff, Timothy J. Hohman, Sarah M. Neuner, Carolyn S. Akers, Nicole C. Weitzel, Alena Shostak, Shawn M. Ferguson, Bret Mobley, David A. Bennett, Julie A. Schneider, Angela L. Jefferson, Catherine C. Kaczorowski, Matthew S. Schrag
Summary: PLD3 is a lysosomal phospholipase D that plays a role in AD and cognition. PLD3 expression levels are associated with beta-amyloid plaque density and cognitive decline.
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
Pharmacology & Pharmacy
Samira Geravand, Manizheh Karami, Hedayat Sahraei, Fardin Rahimi
Summary: There is evidence to suggest that high intake of aluminum is associated with an increased risk of dementia or cognitive decline. In this study, L-arginine was injected into the dorsal hippocampus of an Alzheimer's model induced by AlCl3. The results showed that L-arginine intervention may be protective against Alzheimer's by increasing hippocampal NO levels.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Xin Chen, Ana Joyce Munoz-Arellano, Dina Petranovic
Summary: UBB+1 accumulation is linked to UPS dysfunction and neurodegeneration, while low UBB+1 expression activates the autophagy pathway and reduces intracellular A beta toxicity.
Article
Clinical Neurology
Shuta Ozawa, Yukiko Hori, Yusuke Shimizu, Atsuhiko Taniguchi, Takanobu Suzuki, Wenbo Wang, Yung Wen Chiu, Reiko Koike, Satoshi Yokoshima, Tohru Fukuyama, Sho Takatori, Youhei Sohma, Motomu Kanai, Taisuke Tomita
Summary: The study demonstrated that photo-oxygenation facilitates the clearance of aggregated amyloid-beta from the brains of living Alzheimer's disease model mice, and enhances the microglial degradation of amyloid-beta peptide, suggesting a novel strategy for Alzheimer's disease treatment that may be compatible with immunotherapy.
Article
Neurosciences
Wei-hao Li, Lin-hua Gan, Fang-fang Ma, Rui-li Feng, Jiao Wang, Yan-hui Li, Yang-yang Sun, Ya-jiang Wang, Xin Diao, Fei-yang Qian, Tie-qiao Wen
Summary: The study found that Dcf1 is involved in A beta aggregation, and inhibiting Dcf1 expression can reduce A beta deposition, thereby alleviating the decline in cognitive ability and memory loss in AD patients.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Cell Biology
Bong-Geum Jang, Boyoung Choi, Suyeon Kim, Duk-Shin Lee, Jisun Lee, Young Ho Koh, Sangmee Ahn Jo, Ji-Eun Kim, Tae-Cheon Kang, Min-Ju Kim
Summary: The study found that 2,4-diacetylphloroglucinol (DAPG) can effectively reduce beta-amyloid (A beta) levels by regulating pathways and molecular interactions associated with A beta. This finding has significant implications for the treatment of Alzheimer's disease (AD).
Article
Biochemistry & Molecular Biology
Massimiliano Cuccioloni, Valentina Cecarini, Laura Bonfili, Riccardo Pettinari, Alessia Tombesi, Noemi Pagliaricci, Laura Petetta, Mauro Angeletti, Anna Maria Eleuteri
Summary: Alzheimer's disease is a fatal neurodegenerative disorder characterized by severe dementia and irreversible memory loss. The aggregation of amyloid-beta peptides in the central nervous system plays a critical role in the disease. In this study, an organoruthenium derivative of curcumin was found to inhibit the formation and limit the size of amyloid aggregates. It also showed less toxicity to neuronal cells and protected them from amyloid toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Junsoo Bok, Juchan Ha, Bum Ju Ahn, Yongwoo Jang
Summary: Electroceuticals are electronic neurostimulators used for therapy, specifically targeting neural circuits to achieve precision therapy for Alzheimer's disease (AD). Extensive studies have been conducted on the effects of electroceuticals on beta-amyloid plaques and tau tangles, the pathological molecular markers of AD. This review provides insights into recent technological developments and therapeutic effects of various electronic stimulatory systems for AD, including transcranial direct current stimulation, 40-Hz gamma oscillations, transcranial magnetic stimulation, electromagnetic field stimulation, infrared light stimulation, ionizing radiation therapy, and focused ultrasound.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Multidisciplinary
Zhong-Hao Zhang, Lei Wen, Qiu-Yan Wu, Chen Chen, Rui Zheng, Qiong Liu, Jia-Zuan Ni, Guo-Li Song
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Zhong-Hao Zhang, Qiu-Yan Wu, Chen Chen, Rui Zheng, Yao Chen, Jia-Zuan Ni, Guo-Li Song
Article
Optics
Hongji Liu, Ziwei Zhuang, Jiexing He, Shen Tong, Chen He, Xiangquan Deng, Guoli Song, Ping Qiu, Ke Wang
Article
Biochemistry & Molecular Biology
Rui Zheng, Zhong-Hao Zhang, Yu-Xi Zhao, Chen Chen, Shi-Zheng Jia, Xian-Chun Cao, Li-Ming Shen, Jia-Zuan Ni, Guo-Li Song
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Behavioral Sciences
Tengrui Shi, Yujie Yang, Zhonghao Zhang, Lei Zhang, Jianxi Song, Yongjing Ping, Xiubo Du, Guoli Song, Qiong Liu, Nan Li
NEUROBIOLOGY OF LEARNING AND MEMORY
(2019)
Article
Biochemistry & Molecular Biology
Zhong-Hao Zhang, Chen Chen, Shi-Zheng Jia, Xian-Chun Cao, Min Liu, Jing Tian, Peter R. Hoffmann, Hua-Xi Xu, Jia-Zuan Ni, Guo-Li Song
Summary: The study shows that the Se compound Se-Met can restore synaptic deficits in 3 x Tg-AD mice by modulating calcium influx mediated by synaptic and extrasynaptic NMDARs, indicating a potential functional interaction between SELENOK and NMDARs.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Neurosciences
Chen Chen, Di Xu, Zhong-Hao Zhang, Shi-Zheng Jia, Xian-Chun Cao, Yu-Bin Chen, Guo-Li Song, Man Shing Wong, Hung Wing Li
EXPERIMENTAL NEUROLOGY
(2020)
Review
Neurosciences
Zhong-Hao Zhang, Guo-Li Song
Summary: Selenium and its compounds show potential in preventing and treating Alzheimer's disease, mainly through selenoproteins that play crucial roles in brain function. Analysis of 25 selenoproteins in the brain revealed certain selenoproteins highly expressed in AD-related brain regions, suggesting their involvement in AD pathology. The review discusses the functions of these selenoproteins in AD, indicating new research directions for understanding the mechanism of Selenium in Alzheimer's disease.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Chen Chen, Yao Chen, Zhong-Hao Zhang, Shi-Zheng Jia, Yu-Bin Chen, Shao-Ling Huang, Xin-Wen Xu, Guo-Li Song
Summary: Selenomethionine (Se-Met) improves mitochondrial function in Alzheimer's disease (AD) models by upregulating mitochondrial selenoprotein, promoting mitochondrial fusion or division, restoring mitochondrial membrane potential, enhancing mitochondrial energy metabolism, inhibiting intracellular ROS generation, and reducing apoptosis.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Correction
Geriatrics & Gerontology
Chen Chen, Yao Chen, Zhong-Hao Zhang, Shi-Zheng Jia, Yu-Bin Chen, Shao-Ling Huang, Xin-Wen Xu, Guo-Li Song
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Shi-Zheng Jia, Xin-Wen Xu, Zhong-Hao Zhang, Chen Chen, Yu-Bin Chen, Shao-Ling Huang, Qiong Liu, Peter R. Hoffmann, Guo-Li Song
Summary: Selenoprotein K plays a critical role in regulating intracellular calcium flux, degradation pathways, and response to stress in neurons. Knockout of SELENOK in neurons leads to increased apoptosis, activated cascade pathways, and decreased cognitive ability and increased anxiety in older mice.
Article
Biochemistry & Molecular Biology
Zhong-Hao Zhang, Xian-Chun Cao, Jia-Ying Peng, Shao-Ling Huang, Chen Chen, Shi-Zheng Jia, Jia-Zuan Ni, Guo-Li Song
Summary: This study demonstrates the therapeutic potential of combined supplementation of selenium and folic acid in Alzheimer's disease. The treatment regimen improves synaptic plasticity and cognitive ability by modulating brain lipid metabolism, potentially through antioxidant effects and promoting homocysteine metabolism.
Article
Chemistry, Medicinal
Yazhou Xie, Chen Chen, Shujing Lin, Xi Yu, Shuixian Ye, Xiaojie Chen, Na Ouyang, Wei Xiong, Chenyang Li, Chenshu Xu, Guoli Song, Haiqiang Wu
Summary: Alzheimer's disease (AD) is a multifactorial disease and one of the most common forms of dementia, with limited clinical efficacy of anti-AD drugs. Up-regulated glutaminyl cyclase (QC) and glycogen synthase kinase-3 beta (GSK-3 beta) play critical roles in AD. In this study, novel compounds were designed and synthesized as dual inhibitors targeting QC and GSK-3 beta, and showed significant inhibitory potency on both targets. In vivo studies showed that compound 8 attenuated cognitive deficits and reduced anxiety-like behavior in AD mice by inhibiting QC activity and decreasing GSK-3 beta levels. These compounds have potential as anti-AD agents targeting QC and GSK-3 beta.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Shujing Lin, Chen Chen, Pei Ouyang, Zhiyu Cai, Xibei Liu, Anwar Abdurahman, Jiaying Peng, Yu Li, Zhonghao Zhang, Guo-Li Song
Summary: Our study demonstrates that SELENOM knockout in mice results in decreased synaptic plasticity and memory impairment. Furthermore, SELENOM knockout leads to hyperglycemia and disrupts glucose metabolism, which is crucial for synapse formation and transmission in the brain. The inhibition of the brain insulin signaling pathway is identified as the underlying mechanism for the synaptic deficits and cognitive dysfunction observed in SELENOM knockout mice.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Yinhui Li, Chen Chen, Di Xu, Chung-Yan Poon, See-Lok Ho, Rui Zheng, Qiong Liu, Guoli Song, Hung-Wing Li, Man Shing Wong