Review
Chemistry, Multidisciplinary
Raquel L. Lieberman, Minh Thu Ma
Summary: Glaucoma is a disease caused by protein misfolding, particularly myocilin mutations leading to intracellular aggregation, resulting in elevated intraocular pressure and vision loss. This disorder is associated with dysfunction in the trabecular meshwork and can be compared to amyloid diseases like Alzheimer's and diabetes.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Review
Ophthalmology
Emily G. Saccuzzo, Hannah A. Youngblood, Raquel L. Lieberman
Summary: Mutations in the MYOC gene account for approximately 5% of cases of primary open angle glaucoma (POAG). This review focuses on the molecular understanding of myocilin-associated glaucoma, including the structure and aggregates formed by mutant myocilin. Open questions and translational directions enabled by this work are also discussed.
PROGRESS IN RETINAL AND EYE RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Ivana Sirangelo, Clara Iannuzzi
Summary: The study provides an overview of the molecular effects induced by glycation on the amyloid aggregation process of protein models associated with misfolding diseases. Glycation plays a key role in protein folding, kinetics of amyloid formation, and amyloid cytotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Emily G. Saccuzzo, Mackenzie D. Martin, Kamisha R. Hill, Minh Thu Ma, Yemo Ku, Raquel L. Lieberman
Summary: The study suggests that calcium dysregulation may lead to misfolding of WT myocilin, potentially contributing to the genetic mechanism of early-onset glaucoma. Depletion of calcium causes WT myocilin to misfold and aggregate in the endoplasmic reticulum, resulting in ER stress.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2022)
Review
Cell Biology
Alessandra Bigi, Roberta Cascella, Cristina Cecchi
Summary: The misfolding and aggregation of a-synuclein is the key feature of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies. Soluble oligomeric assemblies formed during the early stages of aggregation are toxic to neurons, while fibrillar conformers contribute to the spreading of the pathology. Recent studies have also shown that a-synuclein fibrils release soluble and highly toxic oligomeric species, leading to immediate dysfunction in recipient neurons. This review discusses the mechanisms of cellular dysfunction caused by a-synuclein oligomers and fibrils in synucleinopathies.
NEURAL REGENERATION RESEARCH
(2023)
Article
Cell Biology
Hailee F. Scelsi, Kamisha R. Hill, Brett M. Barlow, Mackenzie D. Martin, Raquel L. Lieberman
Summary: Accurate prediction of the pathogenicity of mutations associated with genetic diseases is crucial for the success of precision medicine. In this study, missense mutations in the MYOC gene's olfactomedin domain were investigated to determine the disease-causing variants from benign ones. Through cellular and biophysical assays, followed by analysis of biochemical and clinical data, the thermal stability of the olfactomedin domain was found to be a statistically significant metric for distinguishing pathogenic variants. These findings suggest the potential for clinical monitoring of glaucoma through genotyping of the MYOC gene.
DISEASE MODELS & MECHANISMS
(2023)
Review
Biochemistry & Molecular Biology
Liisa Lutter, Liam D. Aubrey, Wei-Feng Xue
Summary: Predicting the highly ordered three-dimensional structures of amyloid protein fibrils from their monomeric self-assembly precursors remains a challenging aspect of the classical protein folding problem, due to the polymorphic nature of amyloid assembly. Understanding the diversity and individuality of amyloid structures, as well as the link to biology and disease phenotypes, is essential. Current research focuses on resolving the structural basis and biological consequences of polymorphic amyloid assemblies using various techniques such as cryo-EM, ssNMR, and AFM.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biophysics
Victoria T. Reichelderfer, Andres F. Chaparro Sosa, Joel L. Kaar, Daniel K. Schwartz
Summary: The interactions between lipid bilayers and insulin can either stabilize or destabilize the protein, preventing or exacerbating the formation of amyloid fibrils.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Ophthalmology
Emi Nakahara, John D. Hulleman
Summary: By using the Gaussia luciferase assay, researchers were able to successfully track the secretion of MYOC variants, indicating that this method could be an effective way to quickly assess the behavior of MYOC variants.
CURRENT EYE RESEARCH
(2022)
Correction
Chemistry, Multidisciplinary
Ritika Sharma, Anchala Kumari, Bishwajit Kundu, Abhinav Grover
Summary: The study demonstrates that epicatechin gallate (ECG) inhibits the amyloid fibrillation of glaucoma associated myocilin protein.
Article
Biochemical Research Methods
Takahiro Watanabe-Nakayama, Kenjiro Ono
Summary: The structural dynamics of amyloid protein aggregation process play a role in neurodegenerative diseases. High-speed atomic force microscopy (HS-AFM) is a useful tool to visualize individual aggregate species. Correction of stage drift in HS-AFM images can be done using free software like ImageJ, allowing for easier analysis of structural dynamics.
Review
Pharmacology & Pharmacy
Michele Vendruscolo
Summary: Protein misfolding diseases, such as Alzheimer's and Parkinson's diseases, have a major impact on our healthcare systems and societies. This paper discusses drug discovery strategies to target protein misfolding and aggregation, including thermodynamic and kinetic approaches. There is a need for disease-modifying treatments to address the over 50 human disorders associated with protein misfolding and aggregation.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Review
Biochemistry & Molecular Biology
Jin-Beom Si, Bokyung Kim, Jin Hae Kim
Summary: TTR is a crucial transporter of thyroid hormone and retinol binding protein in human plasma and cerebrospinal fluid, yet it is also known for its amyloidogenic nature leading to various amyloidoses. Research has shown that decreased stability of TTR's native tetrameric conformation is the main cause of these diseases, and recent multidisciplinary investigations have shed light on the mechanistic details of TTR amyloidogenic transformation. Special emphasis has been placed on identifying novel structural features in amyloidogenic species of TTR and discussing the proteolysis-induced fragmentation mechanism that promotes TTR amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Engineering, Chemical
Yanxian Zhang, Yijing Tang, Dong Zhang, Yonglan Liu, Jian He, Yung Chang, Jie Zheng
Summary: The research focuses on the mechanism of amyloid cross-seeding between Aβ and hIAPP and its connection between AD and T2D, explores the role of structural compatibility and sequence similarity of amyloid proteins in cross-seeding, and proposes current challenges and future research directions in this less-studied field.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2021)
Article
Ophthalmology
Mackenzie D. Martin, Dustin J. E. Huard, Ricardo C. Guerrero-Ferreira, Ishani M. Desai, Brett M. Barlow, Raquel L. Lieberman
Summary: Myocilin, a modular multidomain protein, is widely expressed in the human body but is best known for its presence in the trabecular meshwork extracellular matrix and its association with glaucoma. This study expressed and purified milligram-scale quantities of full-length myocilin, characterized its oligomerization and glycosylation states, and identified new misfolded states and layers of intrinsic heterogeneity, expanding our knowledge of myocilin structure and its biological function.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Laura Y. Kim, Peter M. Thompson, Hyunna T. Lee, Mihir Pershad, Sharon L. Campbell, Gregory M. Alushin
JOURNAL OF MOLECULAR BIOLOGY
(2016)
Article
Nanoscience & Nanotechnology
Tosan Omabegho, Pinar S. Gurel, Clarence Y. Cheng, Laura Y. Kim, Paul V. Ruijgrok, Rhiju Das, Gregory M. Alushin, Zev Bryant
NATURE NANOTECHNOLOGY
(2018)
Article
Biology
Pinar S. Gural, Laura Y. Kim, Paul V. Rujigrok, Tosan Omabegho, Zev Bryant, Gregory M. Alushin
Article
Biochemistry & Molecular Biology
William J. Rice, Anchi Cheng, Alex J. Noble, Edward T. Eng, Laura Y. Kim, Bridget Carragher, Clinton S. Potter
JOURNAL OF STRUCTURAL BIOLOGY
(2018)
Article
Biology
Alex J. Noble, Venkata P. Dandey, Hui Wei, Julia Braschi, Jillian Chase, Priyamvada Acharya, Yong Zi Tan, Zhening Zhang, Laura Y. Kim, Giovanna Scapin, Micah Rapp, Edward T. Eng, William J. Rice, Anchi Cheng, Carl J. Negro, Lawrence Shapiro, Peter D. Kwong, David Jeruzalmi, Amedee des Georges, Clinton S. Potter, Bridget Carragher
Article
Biochemistry & Molecular Biology
Anchi Cheng, Edward T. Eng, Lambertus Alink, William J. Rice, Kelsey D. Jordan, Laura Y. Kim, Clinton S. Potter, Bridget Carragher
JOURNAL OF STRUCTURAL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Laura Y. Kim, William J. Rice, Edward T. Eng, Mykhailo Kopylov, Anchi Cheng, Ashleigh M. Raczkowski, Kelsey D. Jordan, Daija Bobe, Clinton S. Potter, Bridget Carragher
FRONTIERS IN MOLECULAR BIOSCIENCES
(2018)
Article
Physiology
Laura Yaunhee Kim, Matthew C. Johnson, Ingeborg Schmidt-Krey
COMPREHENSIVE PHYSIOLOGY
(2012)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)