Article
Biochemistry & Molecular Biology
Henrik Tonner, Selina Hunn, Nadine Auler, Carsten Schmelter, Vanessa M. Beutgen, Harald D. von Pein, Norbert Pfeiffer, Franz H. Grus
Summary: In this study, intravitreal injection of anti-HMGB1 Ab was found to reduce HMGB1-dependent inflammatory signaling and improve RGC neuronal survival in an experimental animal model of glaucoma. Mass spectrometric analysis demonstrated increased abundance of RNA metabolism-associated hnRNPs in animals injected with the antibody, while microarray analysis showed a decreased expression of inflammatory mediators in the HMGB1 group. These findings suggest that anti-HMGB1 Ab may play a neuroprotective role in glaucoma by modulating inflammatory processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Tonking Bastola, Guy A. Perkins, Keun-Young Kim, Seunghwan Choi, Jin-Woo Kwon, Ziyao Shen, Stefan Strack, Won-Kyu Ju
Summary: AKAP1 is a multifunctional mitochondrial scaffold protein that regulates mitochondrial dynamics, bioenergetics, and calcium homeostasis. Loss of AKAP1 leads to mitochondrial fragmentation and loss of retinal ganglion cells. Modulation of AKAP1 could be a potential therapeutic target for glaucoma and other mitochondria-associated optic neuropathies.
Article
Geriatrics & Gerontology
Emily Machiela, Paige D. Rudich, Annika Traa, Ulrich Anglas, Sonja K. Soo, Megan M. Senchuk, Jeremy M. Van Raamsdonk
Summary: This study in C. elegans models of Huntington's disease reveals that reducing mitochondrial fragmentation by targeting genes other than drp-1 can be protective and improve movement deficits, while disrupting the mitochondrial fission gene drp-1 can have detrimental effects. The research identifies novel therapeutic targets for HD aimed at enhancing mitochondrial health.
Article
Ophthalmology
Bindu Kodati, Dorota L. Stankowska, Vignesh R. Krishnamoorthy, Raghu R. Krishnamoorthy
Summary: The study found that JNK2 plays a major role in endothelin-mediated loss of retinal ganglion cells in mice. The neuroprotective effects in JNK2(-/-) mice following ET-1 administration occur mainly in the soma and not in the axons of RGCs.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Maria Jesus Rodrigo, David Garcia-Herranz, Manuel Subias, Teresa Martinez-Rincon, Silvia Mendez-Martinez, Irene Bravo-Osuna, Ana Carretero, Jesus Ruberte, Julian Garcia-Feijoo, Luis Emilio Pablo, Rocio Herrero-Vanrell, Elena Garcia-Martin
Summary: Comparing two prolonged animal models of glaucoma over 24 weeks, both showed progressive neuroretinal degeneration, with the Ms20/10 model exhibiting a more rapid increase in intraocular pressure and better preservation of ocular surface. Although differences were observed in structural and functional aspects between the two models, both have value for studying glaucoma pathology.
Article
Biochemistry & Molecular Biology
Carsten Schmelter, Kristian Nzogang Fomo, Alina Brueck, Natarajan Perumal, Sascha D. D. Markowitsch, Gokul Govind, Thomas Speck, Norbert Pfeiffer, Franz H. H. Grus
Summary: Glaucoma is a complex optic neuropathy characterized by the loss of retinal ganglion cells (RGCs) and their axons, leading to visual function decline. The exact molecular mechanism of glaucoma remains unclear, and there is an urgent need for therapeutic strategies targeting the neurodegenerative component of this disease. The synthetic CDR1 peptide has shown beneficial effects on RGC viability in a concentration-dependent manner and has been identified as a potential biomarker candidate in glaucoma patients. It specifically interacts with retinal acidic leucine-rich nuclear phosphoprotein 32A (ANP32A) and affects the expression of various proteins related to acetyl-CoA biosynthesis and cytoskeleton regulation. The peptide's interaction with ANP32A's N-terminal leucine-rich repeat (LRR) domain suggests its translational potential for glaucoma treatment.
Review
Biochemistry & Molecular Biology
Sara Al Hussein Al Awamlh, Lauren K. Wareham, Michael L. Risner, David J. Calkins
Summary: Glaucoma, a multifactorial disease managed by lowering intraocular pressure, often leads to vision loss. The degeneration of retinal ganglion cells in glaucoma is similar to neurodegeneration in age-related CNS disorders, highlighting the potential of targeting insulin signaling for neuroprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Sayali Chandrashekhar Deolankar, Mohd Altaf Najar, Poornima Ramesh, Anagha Kanichery, Avinash K. Kudva, Shamprasad Varija Raghu, T. S. Keshava Prasad
Summary: Accumulation of A beta(42) peptides forming plaque in various regions of the brain is a characteristic of Alzheimer's disease progression. However, there is currently no effective management strategy for attenuating the early-stage toxicity induced by A beta(42). This study investigated the neuroprotective effects of aqueous extracts from Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) using a Drosophila melanogaster model. Through quantitative proteomics analysis, the study found that the Brahmi extract restored the expression of a significant portion of differentially expressed proteins in A beta(42)-expressing flies, which are involved in neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also confirmed by negative geotaxis behavioral analysis. These findings provide a platform for developing novel therapies for Alzheimer's disease by elucidating the molecular targets of neuroprotection conferred by the aqueous extracts of Bacopa monnieri or Centella asiatica.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
M. J. Rodrigo, D. Garcia-Herranz, A. Aragon-Navas, M. Subias, T. Martinez-Rincon, S. Mendez-Martinez, M. J. Cardiel, J. Garcia-Feijoo, J. Ruberte, R. Herrero-Vanrell, L. Pablo, E. Garcia-Martin, I Bravo-Osuna
Summary: This study evaluated a new chronic glaucoma model induced by intracameral injection of Dex-PLGA-Ms in rats over six months. The results showed progressive increase in intraocular pressure, subsequent neuroretinal degeneration, and deposition of collagen IV after two injections. This demonstrates the potential of drug delivery systems to induce pathology rather than treat it.
Review
Biochemistry & Molecular Biology
Alessandra Boccaccini, Dario Cavaterra, Carmela Carnevale, Lucia Tanga, Stefano Marini, Alessio Bocedi, Pedro M. Lacal, Gianluca Manni, Grazia Graziani, Diego Sbardella, Grazia Raffaella Tundo
Summary: Neuroprotective therapies have become a modern and challenging approach for the treatment of neurodegenerative diseases. Glaucoma, a neurodegenerative disease affecting millions of people worldwide, lacks effective therapeutic approaches. The adoption of neuroprotective strategies and the exploration of potential drugs for glaucoma treatment are ongoing. This review provides a summary of the rationale behind neuroprotective strategies, the molecular aspects of glaucoma as a neurodegenerative disease, and the examination of promising direct neuroprotective drugs.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jacky M. K. Kwong, Joseph Caprioli, Joanne C. Y. Lee, Yifan Song, Feng-Juan Yu, Jingfang Bian, Ying-Hon Sze, King-Kit Li, Chi-Wai Do, Chi-Ho To, Thomas Chuen Lam
Summary: This study investigated the proteomic changes in the retina after optic nerve transection in rats. Using high-resolution mass spectrometry, they identified several differentially expressed proteins related to retinal ganglion cell damage, such as ALDH1A1 and SNCG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Gulgun Tezel
Summary: Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cells and degeneration of axons. The disease involves multiple triggers, cell types, and molecular pathways, with both intrinsic responses of RGCs and interactions of surrounding glia playing decisive roles in cell fate. Mitochondrial dysfunction and glia-driven neuroinflammation have widespread impacts in the glaucomatous retina and optic nerve, suggesting potential unified treatment strategies to protect RGCs.
Article
Ophthalmology
Maria J. Rodrigo, Teresa Martinez-Rincon, Manuel Subias, Silvia Mendez-Martinez, Luis E. Pablo, Vicente Polo, Alba Aragon-Navas, David Garcia-Herranz, Julian Garcia Feijoo, Irene Bravo Osuna, Rocio Herrero-Vanrell, Elena Garcia-Martin
Summary: This study found that male rats with chronic glaucoma had significantly higher IOP in both models, as well as more severe neuroretinal structure and function damage compared to females. Female rats with chronic glaucoma experienced lower IOP and structural loss, and better neuroretinal functionality than males. Sex and the method of inducing ocular hypertension were found to influence neuroretinal degeneration.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell Biology
Anthony R. Anzell, Garrett M. Fogo, Zoya Gurm, Sarita Raghunayakula, Joseph M. Wider, Kathleen J. Maheras, Katlynn J. Emaus, Timothy D. Bryson, Madison Wang, Robert W. Neumar, Karin Przyklenk, Thomas H. Sanderson
Summary: Mitochondrial dynamics and mitophagy are essential for maintaining a healthy mitochondrial network, and their disruption can lead to mitochondrial dysfunction. Research suggests that these systems are interrelated, but their specific roles in ischemia/reperfusion injury are still unclear. Using a mouse model and evaluating mitochondrial morphology and mitophagic flux, it was found that Drp1 plays a key role in the progression of I/R injury, while mitophagy can occur independently of Drp1-mediated mitochondrial fission.
CELL DEATH & DISEASE
(2021)
Review
Pharmacology & Pharmacy
Lidawani Lambuk, Mohd Aizuddin Mohd Lazaldin, Suhana Ahmad, Igor Iezhitsa, Renu Agarwal, Vuk Uskokovic, Rohimah Mohamud
Summary: This article discusses the neuroprotective role of brain-derived neurotrophic factor (BDNF) in promoting the survival of retinal ganglion cells (RGCs) and its potential application in the management of glaucoma. The article also explores the possibility of using BDNF as a biomarker in neurodegenerative diseases such as glaucoma, as well as the challenges and future strategies.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Funke, Carsten Schmelter, Sascha D. Markowitsch, Natarajan Perumal, Janis C. Heyne, Katharina Bell, Norbert Pfeiffer, Franz H. Grus
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Medicine, General & Internal
Carsten Schmelter, Kristian Nzogang Fomo, Natarajan Perumal, Caroline Manicam, Katharina Bell, Norbert Pfeiffer, Franz H. Grus
JOURNAL OF CLINICAL MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
Vanessa M. Beutgen, Carsten Schmelter, Norbert Pfeiffer, Franz H. Grus
Summary: Autoimmune processes are now recognized as part of the natural maintenance of molecular homeostasis, with natural autoantibodies potentially playing a role in clearing cellular debris and reducing inflammation. The gut microbiome has been linked to the formation of self-reactive antibodies, suggesting a potential link to immunological homeostasis and implications for various diseases. The development and optimization of antibodies present challenges, but targeting biologically active sites for therapeutic applications holds promise for the pharmaceutical industry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Carsten Schmelter, Kristian Nzogang Fomo, Natarajan Perumal, Norbert Pfeiffer, Franz H. Grus
Summary: This study demonstrated for the first time that the synthetic CDR1 peptide significantly inhibited the proteolytic activity of HTRA2, while also identified significant protein interaction partners of HTRA2 in the retina, shedding light on the complex protein interaction networks of HTRA2 in neurological tissues and providing a comprehensive protein catalogue for future research on HTRA2-mediated neurodegeneration.
Article
Biochemistry & Molecular Biology
Henrik Tonner, Selina Hunn, Nadine Auler, Carsten Schmelter, Vanessa M. Beutgen, Harald D. von Pein, Norbert Pfeiffer, Franz H. Grus
Summary: In this study, intravitreal injection of anti-HMGB1 Ab was found to reduce HMGB1-dependent inflammatory signaling and improve RGC neuronal survival in an experimental animal model of glaucoma. Mass spectrometric analysis demonstrated increased abundance of RNA metabolism-associated hnRNPs in animals injected with the antibody, while microarray analysis showed a decreased expression of inflammatory mediators in the HMGB1 group. These findings suggest that anti-HMGB1 Ab may play a neuroprotective role in glaucoma by modulating inflammatory processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carsten Schmelter, Alina Brueck, Natarajan Perumal, Sichang Qu, Norbert Pfeiffer, Franz H. H. Grus
Summary: The glycosylation of proteins is a common post-translational modification that plays important regulatory functions in various biological processes. The study developed a lectin-based affinity method for the enrichment and characterization of tear glycoproteins/glycopeptides, and identified specific N-glycosylation sites using high-resolution mass spectrometry. The results provide valuable information for future studies on tear film and ocular surface-related inflammatory diseases.
