Review
Medicine, Research & Experimental
Zhenyang Liu, Hongwei Gao, Ziyu Zhao, Mengrui Huang, Shengnan Wang, Jiuyu Zhan
Summary: Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for diseases such as type 2 diabetes and obesity. PTP1B inhibitors have the potential to improve insulin receptor sensitivity and treat insulin resistance-related diseases. However, the currently available PTP1B inhibitors have been discontinued due to side effects or low selectivity. This article summarizes recent research on PTP1B inhibitors extracted from natural products and provides new options for designing effective inhibitors.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Sonia Rocha, Mariana Lucas, Vera L. M. Silva, Pedro M. O. Gomes, Artur M. S. Silva, Alberto N. Araujo, Natalia Aniceto, Rita C. Guedes, M. Luisa Corvo, Eduarda Fernandes, Marisa Freitas
Summary: This study evaluated a library of 22 pyrazole compounds against human PTP1B activity, identifying two potent inhibitors and highlighting the importance of additional benzene rings in enhancing PTP1B inhibition. The most active compounds showed selectivity over TCPTP and molecular docking analyses revealed key residue contacts. This study represents a significant step in the design of novel PTP1B inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Oncology
Pei-Jie Chen, Yun-Tian Zhang
Summary: Tyrosine phosphorylation is a reversible process regulated by protein tyrosine kinases and phosphatases. Abnormalities in these proteins, such as PTP1B, can contribute to the development of diseases including cancer. Recent studies have shown that PTP1B plays an important role in cancer initiation and progression, making it a potential target for cancer therapies. This review focuses on the functions and pharmacological effects of PTP1B in different types of cancer.
CURRENT CANCER DRUG TARGETS
(2022)
Article
Cell Biology
Zhe Qian, Dongyan Song, Jonathan J. Ipsaro, Carmelita Bautista, Leemor Joshua-Tor, Johannes T. -H. Yeh, Nicholas K. Tonks
Summary: In this study, the researchers generated a novel monoclonal antibody, RD-43, which targeted the ectodomain of PTPRD to inhibit its function and promote its degradation. Treatment with RD-43 was found to suppress SRC signaling required for breast cancer cell invasion. These findings suggest that antibodies targeting extracellular segments of receptor protein tyrosine phosphatases may have therapeutic potential.
GENES & DEVELOPMENT
(2023)
Review
Cell Biology
Michel L. Tremblay
Summary: In this study, a monoclonal antibody targeting PTPRD was identified, which induced dimerization and inhibition of the phosphatase activities of PTPRD and led to its proteolysis by intracellular degradation pathways. This finding opens up a new framework for the clinical manipulation of PTPRD and its closely related family members.
GENES & DEVELOPMENT
(2023)
Review
Medicine, Research & Experimental
Tapan Behl, Amit Gupta, Aayush Sehgal, Ali Albarrati, Mohammed Albratty, Abdulkarim M. Meraya, Asim Najmi, Saurabh Bhatia, Simona Bungau
Summary: Type 2 diabetes is a widely spread metabolic disorder with limitations in conventional therapies. Protein tyrosine phosphatase is a promising therapeutic target, and various inhibitors have shown effectiveness in managing diabetes.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Miriam Diaz-Rojas, Huzefa Raja, Martin Gonzalez-Andrade, Jose Rivera-Chavez, Manuel Rangel-Grimaldo, Isabel Rivero-Cruz, Rachel Mata
Summary: Three undescribed compounds, named alboluteins A-C, were isolated from solid rice-based cultures of Malbranchea albolutea. These compounds showed inhibitory activity against PTP1B, with albolutein C behaving as a noncompetitive inhibitor. Docking and molecular dynamic studies indicated that the compounds prefer to bind at the allosteric site of the enzyme, providing insights into their mechanism of action.
Article
Chemistry, Organic
Yingjun Li, Ledi Lin, Kun Jin, Lixin Gao, Li Sheng, Jihong Liu, Jia Li
Summary: A series of novel arylaminoacetylhydrazone derivatives containing carbazole moiety were designed and synthesized for their potent inhibitory activity against PTP1B, with compound 3t showing the highest activity. Molecular docking was used to study the binding of compound 3t with PTP1B enzyme.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Orathai Saeting, Kasemsiri Chandarajoti, Angsuma Phongphisutthinan, Parichat Hongsprabhas, Sudathip Sae-tan
Summary: The study demonstrated that mungbean water extract increased cellular glucose uptake and improved insulin sensitivity of insulin-resistant HepG2 cells by inhibiting PTP-1B and modulating the expression of genes related to glucose metabolism. This suggests that mungbean water extract has the potential to be a functional ingredient for diabetes.
Article
Biochemistry & Molecular Biology
Ming-Fo Hsu, Yoshihiro Ito, Jai Prakash Singh, Shu-Fang Hsu, Alan Wells, Kuang-Yu Jen, Tzu-Ching Meng, Fawaz G. Haj
Summary: This study identified alpha-actinin4 as a novel substrate of PTP1B in podocytes and demonstrated their interaction in regulating podocyte function. Targeting PTP1B and alpha-actinin4 could be a potential therapeutic approach for podocyte injury.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Daopeng Tan, Jianmei Wang, Xianting Wang, Lin Qin, Yimei Du, Changkuo Zhao, Peijun Liu, Qianru Zhang, Feifei Ma, Jian Xie, Di Wu, Yuqi He
Summary: This study evaluated the inhibitory activity of five new and four known compounds isolated from Gynostemma pentaphyllum on PTP1B, a key factor and regulator of glucose and lipid metabolism. The results showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship indicated that the strength of PTP1B inhibitory activity was mainly related to the presence of an electron-donating group on its side chain.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biology
Sofija Jovanovic Stojanov, Ana Kostic, Mila Ljujic, Ema Lupsic, Silvia Schenone, Milica Pesic, Jelena Dinic
Summary: Drug resistance is a major challenge in treating glioblastoma. Autophagy plays a crucial role in drug resistance, and the use of autophagy inhibitors can enhance the effectiveness of targeted therapy. This study shows that two Src tyrosine kinase inhibitors can induce autophagy in glioblastoma cells, and inhibiting autophagy can increase the anticancer effects of these inhibitors.
Article
Biochemistry & Molecular Biology
Anderly C. Chueh, Gahana Advani, Momeneh Foroutan, Jai Smith, Nadia Ng, Harshal Nandurkar, Daisy S. Lio, Hong-Jian Zhu, Yuh-Ping Chong, Heather Verkade, Donald J. Fujita, Jeffrey Bjorge, Faiza Basheer, Jet Phey Lim, Ian Luk, Amardeep Dhillon, Anuratha Sakthianandeswaren, Dmitri Mouradov, Oliver Sieber, Frederic Hollande, John M. Mariadason, Heung-Chin Cheng
Summary: The study reveals that downregulation of CHK/MATK expression in CRC cells is associated with promoter hypermethylation, leading to hyperactivation of SFKs and enhanced tumorigenic activity. Restoring CHK/MATK expression reduces SFK activity, inhibiting proliferation and migration of colorectal cancer cells in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Yuri N. Chirgadze, Kevin P. Battaile, Ilya Likhachev, Nikolay K. Balabaev, Roni D. Gordon, Vladimir Romanov, Andres Lin, Robert Karisch, Robert Lam, Max Ruzanov, Evgeniy Brazhnikov, Emil F. Pai, Benjamin G. Neel, Nickolay Y. Chirgadze
Summary: In this study, crystal structures of PTP1B apo-enzyme and a complex with a newly identified allosteric inhibitor were presented. The inhibitor binding site is located 18A away from the active center, causing significant rearrangements in the enzyme's active center. Signals from the inhibitor were found to transfer to the catalytic area through dynamic fluctuations of protein structure.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Food Science & Technology
Ting Xiao, Yuan Zhi, Fangfang Tian, Feilong Huang, Xingyan Cheng, Ai Wu, Ling Tao, Zhenghong Guo, Xiangchun Shen
Summary: This study aimed to investigate the ameliorative effect of black raspberry anthocyanins (BRAs) on diabetes retinopathy (DR) and the underlying inhibition mechanism of protein tyrosine phosphatase 1B (PTP1B)-endoplasmic reticulum stress (ERS). The results showed that BRAs significantly improved the disarrangement of retinas and decreased TC and TG levels. Additionally, BRAs effectively improved cell morphology, mitochondrial membrane potential, and decreased apoptosis rates, PTP1B and Caspase-1 activities, and reactive oxygen species levels. Furthermore, BRAs exhibited a strong combination with GRP78 and suppressed the protein expression of the PTP1B-ERS axis.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Biochemistry & Molecular Biology
Soumalya Sarkar, Vivek K. Gupta, Samridhi Sharma, Ting Shen, Veer Gupta, Mehdi Mirzaei, Stuart L. Graham, Nitin Chitranshi
Summary: Alterations in RXR signalling are associated with neurodegenerative disorders. This study identified deleterious SNPs that affect the structure and function of RXR isoforms. Seven missense mutations were found in RXR isoforms, including two novel mutations. In silico prediction tools were used to assess the pathogenicity and stability of RXR mutations. The analysis showed a mix of conclusive and inconclusive genotype-phenotype correlations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Deep Shikha Sharma, Sheetu Wadhwa, Monica Gulati, Bimlesh Kumar, Nitin Chitranshi, Vivek Kumar Gupta, Mohammed Alrouji, Sharif Alhajlah, Othman AlOmeir, Sukriti Vishwas, Rubiya Khursheed, Sumant Saini, Ankit Kumar, Shaik Rahana Parveen, Gaurav Gupta, Flavia Zacconi, Dinesh Kumar Chellappan, Andrew Morris, Raimar Loebenberg, Kamal Dua, Sachin Kumar Singh
Summary: Diabetic retinopathy is a chronic complication of diabetes characterized by damage to retinal blood vessels and potential loss of vision. Current treatment strategies are expensive, invasive, and require specialized administration. This study explores the development of a non-invasive topical formulation that can penetrate deep into the retina, treat damaged vessels, and provide sustained release. Novel drug delivery systems have shown success in treating diabetic retinopathy, and in this study, chitosan modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared and optimized.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Devaraj Basavarajappa, Vivek Gupta, Roshana Vander Wall, Veer Gupta, Nitin Chitranshi, Seyed Shahab Oddin Mirshahvaladi, Viswanthram Palanivel, Yuyi You, Mehdi Mirzaei, Alexander Klistorner, Stuart L. Graham
Summary: Glaucoma is a complex neurodegenerative disease characterized by optic nerve damage and apoptotic retinal ganglion cell (RGC) death. Our study demonstrated that activation of neuronal S1PR1 with siponimod treatment can exert neuroprotection in glaucoma by upregulating Akt and Erk1/2 activation and suppressing the apoptotic signaling via modulation of the c-Jun/Bim cascade and increasing Bad phosphorylation. Conversely, deletion of S1PR1 in RGCs diminished the neuroprotective effects of siponimod treatment. These findings suggest that S1PR1 is a potential therapeutic target for neuroprotection in glaucoma.
Article
Cell Biology
Devaraj Basavarajappa, Vivek Gupta, Nitin Chitranshi, Roshana Vander Wall, Rashi Rajput, Kanishka Pushpitha, Samridhi Sharma, Mehdi Mirzaei, Alexander Klistorner, Stuart Graham
Summary: The S1PR1 signaling pathway plays a crucial role in the survival of retinal ganglion cells and neurons in the dorsolateral geniculate nucleus. Siponimod, as a modulator of S1PR1, exerts direct neuroprotective effects in neurons in the central nervous system, independent of its peripheral immunomodulatory effects.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Yosef Koronyo, Altan Rentsendorj, Nazanin Mirzaei, Giovanna C. Regis, Julia Sheyn, Haoshen Shi, Ernesto Barron, Galen Cook-Wiens, Anthony R. Rodriguez, Rodrigo Medeiros, Joao A. Paulo, Veer B. Gupta, Andrei A. Kramerov, Alexander V. Ljubimov, Jennifer E. Van Eyk, Stuart L. Graham, Vivek K. Gupta, John M. Ringman, David R. Hinton, Carol A. Miller, Keith L. Black, Antonino Cattaneo, Giovanni Meli, Mehdi Mirzaei, Dieu-Trang Fuchs, Maya Koronyo-Hamaoui
Summary: Pathologies of Alzheimer’s disease (AD) can be found in the neurosensory retina, but their exact nature and distribution in relation to disease progression in the brain are still largely unknown. This study conducted extensive histopathological and biochemical investigations of postmortem retina and brain tissues from 86 human donors to better understand the pathological features of AD in the retina. The findings suggest a quantitative relationship between retinopathy, brain pathology, and cognitive impairment, and may lead to the development of reliable retinal biomarkers for noninvasive screening and monitoring of AD.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Haoshen Shi, Yosef Koronyo, Dieu-Trang Fuchs, Julia Sheyn, Ousman Jallow, Krishna Mandalia, Stuart L. Graham, Vivek K. Gupta, Mehdi Mirzaei, Andrei A. Kramerov, Alexander V. Ljubimov, Debra Hawes, Carol A. Miller, Keith L. Black, Roxana O. Carare, Maya Koronyo-Hamaoui
Summary: This study found that vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients, and these deposits were linked to disease status. The study also revealed that the components of retinal vascular tight junctions (TJs) and Aβ expression were correlated with neuropathology. The severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 were identified in MCI and AD patients, which correlated with arteriolar Aβ(40) deposition and cerebral pathology and cognitive deficits.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biotechnology & Applied Microbiology
Nitin Chitranshi, Rashi Rajput, Angela Godinez, Kanishka Pushpitha, Mehdi Mirzaei, Devaraj Basavarajappa, Veer Gupta, Samridhi Sharma, Yuyi You, Giovanna Galliciotti, Ghasem H. Salekdeh, Mark S. Baker, Stuart L. Graham, Vivek K. Gupta
Summary: Our research shows that oxidation deactivation impairs the inhibitory activity of the serine protease inhibitor neuroserpin (NS) in glaucoma. The loss of NS is detrimental to retinal structure and function, and perturbations in autophagy and microglial and synaptic markers are associated with NS ablation. On the other hand, upregulation of NS promotes retinal ganglion cell (RGC) survival and protects against glaucoma-induced degeneration.
Article
Neurosciences
Faezeh Shekari, Morteza Abyadeh, Anna Meyfour, Mehdi Mirzaei, Nitin Chitranshi, Vivek Gupta, Stuart L. Graham, Ghasem Hosseini Salekdeh
Summary: A large number of people around the world suffer from visual impairment, and the available therapies focus on preventing the progression of eye disorders. This review explores the potential of using extracellular vesicles (EVs) as a regenerative therapy for eye-related complications. The review examines the current knowledge about EVs and their therapeutic applications, as well as the challenges in translating EV-based therapy into clinical settings.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Liting Deng, Vivek Gupta, Morteza Abyadeh, Nitin Chitranshi, Kanishka Pushpitha, Yunqi Wu, Veer Gupta, Yuyi You, Joao A. Paulo, Stuart L. Graham, Mehdi Mirzaei, Paul A. Haynes
Summary: Photoreceptor cells are highly vulnerable to oxidative stress, which plays a key role in ocular diseases leading to retinal degeneration and blindness. A mass-spectrometric study using TMT labelling revealed proteome changes in photoreceptor cells following oxidative stress induction. Differential expression of proteins involved in various pathways was observed in response to oxidative stress, including ECM receptor interaction, oxidative phosphorylation, and spliceosome pathways.
Article
Clinical Neurology
Jessica Alber, Femke Bouwman, Jurre den Haan, Robert A. Rissman, Lies De Groef, Maya Koronyo-Hamaoui, Imre Lengyel, Dietmar Rudolf Thal
Summary: Emerging evidence suggests that amyloid beta protein (A beta) and tau-related lesions in the retina are associated with Alzheimer's disease (AD). However, there is inconsistency in the literature regarding these histopathological and in vivo imaging findings, partly due to variability in methods and interpretation across different studies.
ALZHEIMERS & DEMENTIA
(2023)
Article
Medicine, General & Internal
Samran Sheriff, Ting Shen, Danit Saks, Angela Schultz, Heather Francis, Wei Wen, Jiyang Jiang, Mehdi Mirzaei, Veer Gupta, Maria Fiatarone Singh, Perminder S. Sachdev, Stuart L. Graham, Vivek Gupta
Summary: This study investigated the relationship between the APOE epsilon 4 allele and retinal structural and vascular characteristics in older adults. The results suggest that individuals with the APOE epsilon 4 allele may have retinal abnormalities associated with cognitive decline.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Geriatrics & Gerontology
Zhuang-Yao D. Wei, Ketty Liang, Ashok K. Shetty
Summary: SARS-CoV-2 uses a spike protein to enter human cells by binding to ACE-2, resulting in COVID-19. COVID-19 primarily causes respiratory infection and can lead to severe systemic inflammation. Neurological symptoms are also common in some patients.
Review
Biochemistry & Molecular Biology
Devaraj Basavarajappa, Caridad Galindo-Romero, Vivek Gupta, Marta Agudo-Barriuso, Veer B. Gupta, Stuart L. Graham, Nitin Chitranshi
Summary: In this review, the recent research progress on the degenerative mechanisms of retinal ganglion cells (RGCs) in glaucoma is discussed. High intraocular pressure is not the sole factor contributing to glaucoma pathogenesis. The balance of pro-survival and pro-death signaling pathways in the retina strongly influences RGC function and survival. Various molecules and regulated cell death pathways are involved in the development of glaucoma.
MOLECULAR ASPECTS OF MEDICINE
(2023)