Article
Ophthalmology
Matthew M. Harper, Erin A. Boese, Randy H. Kardon, Johannes Ledolter, Markus H. Kuehn
Summary: There was no significant difference in the expression of BDNF and TrkB between glaucomatous and control retinas, but BDNF expression was associated with the use of prostaglandin analogs, while TrkB expression was correlated with factors such as intraocular pressure, drug usage, and treatment outcomes.
CURRENT EYE RESEARCH
(2021)
Article
Neurosciences
Sudhirkumar Yanpallewar, Gianluca Fulgenzi, Francesco Tomassoni-Ardori, Colleen Barrick, Lino Tessarollo
Summary: The pathophysiology of ALS, caused by motoneuron degeneration, is largely unknown. Insufficient neurotrophic support has been suggested as one of the causes of motoneuron cell death. Deleting the BDNF receptor TrkB.T1 in ALS animal models delays cell death and muscle weakness, but does not affect the inflammatory state in the mutant spinal cord.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Mojdeh Abbasi, Vivek K. Gupta, Nitin Chitranshi, Veer Gupta, Reza Ranjbaran, Rashi Rajput, Kanishka Pushpitha, K. B. Devaraj, Yuyi You, Ghasem Hosseini Salekdeh, Robert G. Parton, Mehdi Mirzaei, Stuart L. Graham
Summary: The study shows that silencing of Shp2 has protective effects on RGCs in glaucomatous conditions, and this protection is dependent on Cav-1, suggesting interactions between these two proteins in the retina which result in improvements in inner retinal function and structure.
Review
Geriatrics & Gerontology
Mojdeh Abbasi, Vivek Gupta, Nitin Chitranshi, Petros Moustardas, Reza Ranjbaran, Stuart L. Graham
Summary: Glaucoma is a common retinal disorder characterized by progressive optic nerve damage, leading to visual impairment and potential blindness. Elevated intraocular pressure is a major risk factor, but some patients continue to experience disease progression despite lowering the intraocular pressure. Recent research suggests that Cav-1 protein is involved in signaling pathways and its absence impairs retinal function. The interaction between Cav-1 and the BDNF/TrkB signaling pathway in retinal ganglion cells plays a critical role in their health and protection against apoptosis, which can shed light on glaucoma pathogenesis and potential therapeutic targets.
Article
Multidisciplinary Sciences
Zhiyong Xu, Chunyi Guo, Qiaoli Ye, Yueli Shi, Yihui Sun, Jie Zhang, Jiaqi Huang, Yizhou Huang, Chunlai Zeng, Xue Zhang, Yuehai Ke, Hongqiang Cheng
Summary: The deletion of SHP2 in endothelial cells impairs tumor growth and angiogenesis through the ASK1-c-Jun-SOX7 signaling axis, leading to vascular normalization in tumors. This suggests that targeting SHP2 in tumor-associated endothelial cells could be a promising anti-angiogenic strategy for cancer therapy.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Marialuisa Aragona, Caterina Porcino, Maria Cristina Guerrera, Giuseppe Montalbano, Rosaria Laura, Marzio Cometa, Maria Levanti, Francesco Abbate, Teresa Cobo, Gabriel Capitelli, Jose A. Vega, Antonino Germana
Summary: This review provides an update on the distribution and functions of the BDNF-TrkB system in the sensory organs of zebrafish, highlighting its significance in fish.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychology, Biological
Jian-Feng Fan, Zeng-Hui Tang, Shi-Yi Wang, Si Lei, Bo Zhang, Shao-Wen Tian
Summary: In addition to its antidepressant properties, ketamine has been found to influence memory acquisition, consolidation, and reconsolidation. Administering ketamine immediately after reactivation significantly improves memory reconsolidation, while administering it 6 hours later is not effective. ANA-12, a BDNF TrkB receptor antagonist, reduces the ketamine-induced improvement in memory reconsolidation, although it has no significant effect on hippocampal BDNF levels.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Multidisciplinary Sciences
Muhammad Shahab, Shahin Shah Khan, Maryam Zulfat, Yousef A. Bin Jardan, Amare Bitew Mekonnen, Mohammed Bourhia, Guojun Zheng
Summary: Cancer is a leading cause of death, with an estimated 9.6 million deaths in 2018, and around 500,000 deaths from cancer annually in the United States alone. The SHP2 enzyme plays a key role in cell regulation and its dysregulation is associated with oncogenesis. In this study, we designed peptide inhibitors against SHP2 mutant and identified mutations that enhanced binding affinity. Molecular dynamics simulations and energy calculations confirmed the stability and improved binding affinity of the mutated peptide. Our findings suggest that our proposed peptide may inhibit SHP2 and prevent cancer metastasis.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Wei Wei, Mitchell J. J. Geer, Xinyi Guo, Igor Dolgalev, Neville E. E. Sanjana, Benjamin G. G. Neel
Summary: SHP2 acts as an upstream regulator of RAS activation. Through CRISPR/Cas9 screening, LZTR1, MAP4K5, SPRED2/STK40, and INPPL1 were identified as novel genes associated with SHP2 resistance. Understanding the mechanisms of SHP2 resistance and identifying potential combination therapies is important for overcoming drug resistance in cancer treatment.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Plinio C. Casarotto, Mykhailo Girych, Senem M. Fred, Vera Kovaleva, Rafael Moliner, Giray Enkavi, Caroline Biojone, Cecilia Cannarozzo, Madhusmita Pryiadrashini Sahu, Katja Kaurinkoski, Cecilia A. Brunello, Anna Steinzeig, Frederike Winkel, Sudarshan Patil, Stefan Vestring, Tsvetan Serchov, Cassiano R. A. F. Diniz, Liina Laukkanen, Iseline Cardon, Hanna Antila, Tomasz Rog, Timo Petteri Piepponen, Clive R. Bramham, Claus Normann, Sari E. Lauri, Mart Saarma, Ilpo Vattulainen, Eero Castren
Summary: The study reveals that antidepressant drugs bind directly to the TRKB receptor, facilitating its activation at the synapse and potentially explaining the mechanism behind antidepressant action.
Article
Immunology
Yara T. Mohamed, Abeer Salama, Mostafa A. Rabie, Mai A. Abd El Fattah
Summary: Activation of TLR-4 and IL-17R leads to neuroinflammatory status, causing dopaminergic neuronal loss in Parkinson's disease. Secukinumab, a monoclonal antibody against IL-17A, reduces IL-17-driven neuroinflammation and improves motor impairment in rotenone-induced PD rats, potentially through inhibiting the activation of TLR-4 and activating the neuro-survival axis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Neurosciences
Jing Wang, Yichen Cai, Jingyi Sun, Hua Feng, Xiaoyu Zhu, Qian Chen, Feng Gao, Qingbin Ni, Leilei Mao, Mingfeng Yang, Baoliang Sun
Summary: In this study, non-invasive treatment methods using AAV vectors carrying BDNF or TrkB genes were performed on stroke-injured rats. The combination therapy significantly improved upper limb motor functional recovery and neurotransmission efficiency, promoting axonal remodeling and restoration of synaptic structures.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Immunology
Samuel Fleury, Imane Boukhatem, Jessica Le Blanc, Melanie Welman, Marie Lordkipanidze
Summary: Platelets and neurons share many similarities in terms of secretory mechanisms and neurotransmitter regulation, with platelets serving as a potential peripheral biomarker for neuronal pathologies due to their high levels of brain-derived neurotrophic factor (BDNF). Despite the abundance of BDNF in platelets, discrepancies in the detection of BDNF receptors on platelets, such as TrkB and p75(NTR), suggest caution in using antibody-based assays for studying neurological disorders. Rigorous characterization of antibodies and bioassays is crucial to understanding the relationship between platelet and neuronal biology of BDNF.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pietro Cacialli, Serena Ricci, Maurizio Lazzari, Liliana Milani, Valeria Franceschini
Summary: Neurotrophins and their receptors have vital roles in the nervous systems of vertebrates. Our study used the zebrafish as a model to examine the mRNA localization patterns of neurotrophins and receptors in the spinal cord. Through qPCR and in situ hybridization, we identified the transcription patterns of each neurotrophin/receptor pathway. Our findings reveal that ngf/trka are the most highly transcribed members in the adult zebrafish spinal cord.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zhijian Jin, Yifan Lu, Xiongyan Wu, Tao Pan, Zhenjia Yu, Junyi Hou, Airong Wu, Jianfang Li, Zhongyin Yang, Chen Li, Min Yan, Chao Yan, Zhenggang Zhu, Bingya Liu, Weihua Qiu, Liping Su
Summary: In this study, anlotinib inhibited gastric cancer (GC) cell growth by inducing apoptosis and G2/M phase arrest in a dose- and time-dependent manner. The interaction between epithelial and stromal cells in the tumor microenvironment affects the response of GC cells to anlotinib. Secreted lactate from GC cells activates cancer-associated fibroblasts (CAFs) to produce BDNF in a NF-kappa B-dependent manner, reducing the sensitivity of GC cells to anlotinib. Targeting the BDNF-TrkB pathway increased the sensitivity of GC cells to anlotinib in a human patient-derived organoid model.
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
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
Cell Biology
Samran Sheriff, Ting Shen, Sandra Abdal, Danit Saks, Mehdi Mirzaei, Veer Gupta, Nitin Chitranshi, Yuyi You, Angela Schultz, Stuart Graham, Vivek Gupta
Summary: Examining retinal tissue provides a unique method to quantify Alzheimer's disease-related changes. This meta-analysis investigated optical coherence tomography parameters and discovered that Alzheimer's disease patients had lower retinal nerve fiber layer thickness and thinner macular parameters compared to controls. Optical coherence tomography angiography parameters showed mixed results between Alzheimer's disease and controls. Overall, our findings suggest that optical coherence tomography technology can detect retinal and microvascular changes in Alzheimer's disease patients and aid in monitoring and early diagnosis.
NEURAL REGENERATION RESEARCH
(2023)
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
Ophthalmology
Danit G. Saks, Angela Schulz, Ayub Qassim, Henry Marshall, Alex W. Hewitt, Stuart Macgregor, Jamie E. Craig, Stuart L. Graham
Summary: Individuals with a higher genetic risk of glaucoma are more likely to have retinal vascular defects and structural glaucomatous loss, but this is not related to systemic cardiovascular risk.
ACTA OPHTHALMOLOGICA
(2023)
Article
Neurosciences
Devaraj Basavarajappa, Vivek Gupta, Nitin Chitranshi, Deepa Viswanathan, Veer Gupta, Roshana Vander Wall, Viswanthram Palanivel, Mehdi Mirzaei, Yuyi You, Alexander Klistorner, Stuart L. Graham
Summary: Glaucoma is a major cause of permanent blindness worldwide, characterized by neurodegeneration and neuroinflammation. Siponimod, an immunomodulatory drug, has shown protective effects against acute NMDA excitotoxicity in the retina. Activation of glial cells, inflammatory pathways, and the NLRP3 inflammasome were suppressed with siponimod treatment. These findings suggest that siponimod has anti-inflammatory effects and could be a potential therapeutic strategy for neuroinflammatory conditions.
MOLECULAR NEUROBIOLOGY
(2023)
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)
