Article
Oncology
Tyler R. McCaw, Evelyn Inga, Herbert Chen, Renata Jaskula-Sztul, Vikas Dudeja, James A. Bibb, Bin Ren, J. Bart Rose
Summary: Gamma secretase inhibitors (GSIs), originally developed as Alzheimer's therapies, have been repurposed as anticancer agents due to their ability to inhibit Notch receptor cleavage. Despite showing promise in preclinical models, GSIs have not demonstrated significant clinical benefit in most solid tumors. Further research is needed to address limitations in understanding GSI mechanisms and improve their efficacy in cancer treatment.
Article
Biochemistry & Molecular Biology
Iowis Zhu, Raymond Liu, Julie M. Garcia, Axel Hyrenius-Wittsten, Dan Piraner, Josef Alavi, Divya Israni, Bin Liu, Ahmad S. Khalil, Kole T. Roybal
Summary: Synthetic biology has the potential to meet clinical requirements by precisely controlling cell function. By systematically engineering key domains involved in regulated intramembrane proteolysis, researchers have developed synthetic intramembrane proteolysis receptors (SNIPRs) that have tunable sensing and transcriptional response abilities. Engineering human primary T cells with this receptor platform demonstrates its therapeutic potential.
Article
Chemistry, Medicinal
Jiachen Wen, Dan Liu, Linxiang Zhao
Summary: Gamma-secretase is a large transmembrane protein complex consisting of four distinct units, which has garnered attention for its role in intramembrane proteolysis. The recent discovery of its atomic structure through cryo-EM has enhanced our understanding of its physiological functions and facilitated the development of novel molecules targeting gamma-secretase. This review focuses on the latest progress of gamma-secretase inhibitors and modulators in clinical and preclinical stages, as well as their potential applications in various biological indications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Clinical Neurology
David M. Peereboom, Xiaobu Ye, Tom Mikkelsen, Glenn J. Lesser, Frank S. Lieberman, H. Ian Robins, Manmeet S. Ahluwalia, Andrew E. Sloan, Stuart A. Grossman
Summary: RO4929097 showed no activity in recurrent GBM patients and demonstrated minimal inhibition of neurosphere formation in fresh tissue samples.
Article
Biochemistry & Molecular Biology
Atul Kumar Singh, Mohd Shuaib, Kumari Sunita Prajapati, Shashank Kumar
Summary: The study reveals that rutin can inhibit the notch signaling pathway and reduce the stemness/self-renewal property in colon cancer cells and colonospheres by targeting gamma secretase.
Article
Biochemistry & Molecular Biology
Prasoon Agarwal, Aleksandra Glowacka, Loay Mahmoud, Wesam Bazzar, Lars-Gunnar Larsson, Mohammad Alzrigat
Summary: Amplification of the MYCN oncogene in neuroblastoma is associated with high-risk disease and poor prognosis. This study reveals that MYCN-amplified neuroblastoma cells have reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. Genes encoding gamma-secretase complex subunits, known for their role in NOTCH signaling, are down-regulated in MYCN-amplified neuroblastoma. Depletion of MYCN or inhibition of gamma-secretase activity restores the expression of gamma-secretase and NOTCH-target genes. This study provides insight into the molecular mechanisms underlying MYCN's contribution to high-risk neuroblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sarai Pongjantarasatian, Nunthawan Nowwarote, Varumporn Rotchanakitamnuai, Watcharee Srirodjanakul, Ritmongkol Saehun, Kajohnkiart Janebodin, Jeeranan Manokawinchoke, Benjamin P. J. Fournier, Thanaphum Osathanon
Summary: Notch signaling plays an important regulatory role in oral squamous cell carcinoma (OSCC), promoting cell growth, cell cycle progression, cell migration, and invasion. Blocking Notch signaling can significantly inhibit the proliferation and progression of OSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Atul Kumar Singh, Kumari Sunita Prajapati, Shashank Kumar
Summary: This study demonstrates the potential of hesperidin to bind to the catalytic site of GS and inhibit the Notch signaling pathway, leading to a decrease in cancer stemness and colonosphere formation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Daniel R. Dries, Gang Yu
Summary: Research showed that gamma-secretase is a potential therapeutic target for Alzheimer's disease, and provided new opportunities for treatment.
Article
Pharmacology & Pharmacy
Hui Jia, Mingyue Liu, Xinying Wang, Qiyu Jiang, Shu Wang, Ramesh Kumar Santhanam, Chongning Lv, Qingchun Zhao, Jincai Lu
Summary: The study revealed the significant inhibitory effect of Cimigenoside on breast cancer, suppressing proliferation or metastasis of breast cancer cells by targeting the Notch signaling pathway-mediated mitochondrial apoptosis and EMT process.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Medicine, Research & Experimental
Hui Jia, Zuojun Wang, Jingyi Zhang, Fan Feng
Summary: The gamma-secretase complex plays a crucial role in the activation and regulation of the Notch pathway, which is closely associated with the occurrence and development of various types of tumors. This review provides a detailed description of the basic situation and biological functions of the gamma-secretase complex, as well as its applications in the treatment of breast cancer and liver cancer.
Article
Developmental Biology
Toshiyuki Ohtsuka, Ryoichiro Kageyama
Summary: Hes1 overexpression expands the pool of embryonic NSCs, prolongs the generation of later-born neurons, and leads to the expansion of NSC reservoir in the postnatal and adult brain.
Article
Cell Biology
Junchen Chen, Xiaoxue Dong, Xuejun Cheng, Qiang Zhu, Jinyu Zhang, Qian Li, Xiaoli Huang, Min Wang, Liping Li, Weixiang Guo, Binggui Sun, Qiang Shu, Wen Yi, Xuekun Li
Summary: Ogt deficiency in adult neural stem/progenitor cells leads to a decrease in the aNSPC pool, abnormal neurogenesis, and impaired cognitive function in adult mice. Mechanistic studies reveal that Ogt catalyzes the O-GlcNAc modification of the Notch TM/ICD fragment, which in turn affects neurogenic defects induced by Ogt deficiency.
Article
Dermatology
Siri Hansen Stabell, Anastasia Renzi, Hogne Roed Nilsen, Olaf Harald Antonsen, Johanna Hol Fosse, Guttorm Haraldsen, Olav Sundnes
Summary: Notch signalling plays a crucial role in multiple human diseases, but the activation status of Notch signalling in patients with familial hidradenitis suppurativa (HS) has not been thoroughly studied. This study established immunostaining protocols to identify activated Notch receptors in human skin tissue and confirmed the ability to detect changes in Notch activation using an ex vivo skin organ model. The results showed the distribution of active Notch signalling in human apocrine-bearing skin and demonstrated a reduced activation of Notch in the epidermis of lesional HS.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Biology
Michael Collins, Jean-Marie Michot, Christophe Bellanger, Charlotte Mussini, Karim Benhadji, Christophe Massard, Franck Carbonnel
Summary: Inhibition of Notch oncogenic signaling in humans leads to tumor regression and plays a role in intestinal homeostasis. A study in patients with refractory cancer treated with the first-in-human Notch inhibitor LY3039478 revealed abnormal intestinal epithelial cell differentiation and transient diarrhea as side effects, which resolved after discontinuing the drug. The findings confirm the importance of Notch signaling in maintaining intestinal homeostasis in humans.
Article
Multidisciplinary Sciences
Inwoo Hwang, Chung Kwon Kim, Hyo Rim Ko, Kye Won Park, Sung-Woo Cho, Jee-Yin Ahn
SCIENTIFIC REPORTS
(2016)
Article
Multidisciplinary Sciences
No-Joon Song, Ui Jeong Yun, Sunghee Yang, Chunyan Wu, Cho-Rong Seo, A-Ryeong Gwon, Sang-Ha Baik, Yuri Choi, Bo Youn Choi, Gahee Bahn, Suji Kim, So-Mi Kwon, Jin Su Park, Seung Hyun Baek, Tae Joo Park, Keejung Yoon, Byung-Joon Kim, Mark P. Mattson, Sung-Joon Lee, Dong-Gyu Jo, Kye Won Park
SCIENTIFIC REPORTS
(2016)
Article
Medicine, Research & Experimental
Kangsan Roh, Sungrae Cho, Jae-hyun Park, Byong Chul Yoo, Won-Ki Kim, Seok-ki Kim, Kyewon Park, Hee Kang, Jin-mo Ku, Chang-Hwan Yeom, Kyunghoon Lee, Sukchan Lee
EXPERIMENTAL BIOLOGY AND MEDICINE
(2017)
Article
Pharmacology & Pharmacy
Kangsan Roh, Suji Kim, Hee Kang, Jin-Mo Ku, Kye Won Park, Sukchan Lee
PHARMACOLOGICAL RESEARCH
(2017)
Article
Agriculture, Dairy & Animal Science
Tara R. Price, Kristin Moncada, Hector Leyva-Jimenez, Kye Won Park, Peter Tontonoz, Rosemary L. Walzem
Article
Multidisciplinary Sciences
Eun-Ju Jin, Hyo Rim Ko, Inwoo Hwang, Byeong-Seong Kim, Jeong-Yun Choi, Kye Won Park, Sung-Woo Cho, Jee-Yin Ahn
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Myungsuk Kim, Jisun Lim, Jung-Hee Lee, Kyung-Mi Lee, Suji Kim, Kye Won Park, Chu Won Nho, Yoon Shin Cho
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Suji Kim, No-Joon Song, Gahee Bahn, Seo-Hyuk Chang, Ui Jeong Yun, Jin-Mo Ku, Dong-Gyu Jo, Kye Won Park
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Seo-Hyuk Chang, Ui Jeong Yun, Jin Hee Choi, Suji Kim, A. Reum Lee, Dong Ho Lee, Min-Ju Seo, Vanja Panic, Claudio J. Villanueva, No-Joon Song, Kye Won Park
JOURNAL OF CELLULAR BIOCHEMISTRY
(2019)
Article
Cell Biology
No-Joon Song, Seo-Hyuk Chang, Suji Kim, Vanja Panic, Byung-Hyun Jang, Ui Jeong Yun, Jin Hee Choi, Zhen Li, Ki-Moon Park, Jung-Hoon Yoon, Sunghwan Kim, Jae Hyuk Yoo, Jing Ling, Kirk Thomas, Claudio J. Villanueva, Dean Y. Li, Jee-Yin Ahn, Jin-Mo Ku, Kye Won Park
CELL DEATH & DISEASE
(2018)
Article
Multidisciplinary Sciences
Sungrae Cho, Kangsan Roh, Jaehyun Park, Yong Seok Park, Minji Lee, Seungchan Cho, Eui-Joon Kil, Mun-Ju Cho, Jeong Su Oh, Hee-Seong Byun, Sang-Ho Cho, Kyewon Park, Hee Kang, Jinmo Koo, Chang-Hwan Yeom, Sukchan Lee
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Jin Hee Choi, No-Joon Song, A. Reum Lee, Dong Ho Lee, Min-Ju Seo, Suji Kim, Seo-Hyuk Chang, Dong Kwon Yang, Yu-Jin Hwang, Kyung-A Hwang, Tal Soo Ha, Ui Jeong Yun, Kye Won Park
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Seo-Hyuk Chang, Jeong-Soo Lee, Ui Jeong Yun, Kye Won Park
Summary: Thermogenic adipocytes generate heat by uncoupling mitochondrial respiration, while Nrf2 plays a crucial role in obesity and metabolism. Both activation and inhibition of Nrf2 can suppress obesity and metabolic diseases, and conflicting findings regarding Nrf2 activities contribute to the variance in thermogenesis and energy metabolism.
Article
Biochemistry & Molecular Biology
Tsendsuren Tungalag, Kye Won Park, Dong Kwon Yang
Summary: Oxidative stress plays a significant role in the pathogenesis of heart diseases, and butein exhibits potential antioxidant effects in cardiomyocytes, providing protection against oxidative damage and suggesting its therapeutic potential for cardiac diseases.
Review
Biochemistry & Molecular Biology
No-Joon Song, Seo-Hyuk Chang, Dean Y. Li, Claudio J. Villanueva, Kye Won Park
EXPERIMENTAL AND MOLECULAR MEDICINE
(2017)
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)