Review
Neurosciences
Urmi Sengupta, Rakez Kayed
Summary: This review summarizes the histopathological features of specific protein aggregation in several neurodegenerative diseases and discusses their overlap. It also highlights the synergistic interplay among Aβ, tau, and alpha-Syn in these diseases, suggesting a protein triumvirate.
PROGRESS IN NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Valentina Oliveri
Summary: Due to the increasing prevalence of amyloid diseases, the impact of transition metals, particularly copper ions, on protein aggregation has become a global concern. Copper ions, while playing vital roles in organisms, can disrupt homeostasis and contribute to the development of amyloid diseases by causing toxic protein aggregates, oxidative stress, mitochondrial dysfunction, impaired cellular signaling, inflammation, and cell death. Understanding the imbalance of copper ions and its effects on protein folding and aggregation is crucial for developing targeted therapies.
Article
Geriatrics & Gerontology
Karina Cuanalo-Contreras, Jonathan Schulz, Abhisek Mukherjee, Kyung-Won Park, Enrique Armijo, Claudio Soto
Summary: Accumulation of misfolded protein aggregates is a common event in age-related protein misfolding disorders, and our study shows that this accumulation is significantly increased in aging. Proteins in aged samples have a higher amount of insoluble aggregates compared to young samples, suggesting a role for protein misfolding and aggregation in aging.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Virology
Jiyan Ma, Jingjing Zhang, Runchuan Yan
Summary: The generation of recombinant prions has provided valuable insights into the characteristics and effects of prions. Recombinant prions can exist in various misfolded conformations and have different outcomes when inoculated into wild-type animals. The ability to seed alone is not sufficient to determine prion activity, as authentic prions need to be both heritable and pathogenic. Research on recombinant prions is important for understanding the pathogenesis of prion diseases and the role of misfolded proteins in other neurodegenerative disorders.
Article
Biophysics
Shaopei Li, Kagan Kerman
Summary: Electrochemical biosensors have been utilized in studying biometal-protein interactions in neurodegenerative diseases such as Alzheimer's and Parkinson's. These sensors have shown promise in monitoring conformational changes induced by biometals and identifying disease biomarkers like amyloid-beta and alpha-synuclein.
BIOSENSORS & BIOELECTRONICS
(2021)
Review
Biology
Konstantin Y. Kulichikhin, Oksana A. Malikova, Anastasia E. Zobnina, Natalia M. Zalutskaya, Aleksandr A. Rubel
Summary: Proteinopathy is characterized by the accumulation of aggregates of a specific protein, which can cause different pathologies due to their various conformations and interactions with other proteins. The majority of neuronal proteinopathies are caused by the aggregation of a limited range of amyloidogenic proteins. Therefore, understanding the conformation and interaction of amyloid proteins is crucial for precise disease description.
Article
Biochemistry & Molecular Biology
Guilian Xu, Susan Fromholt, David R. Borchelt
Summary: The amyloid pathology features of Alzheimer's disease can be classified into fibrillary and diffuse. Studies suggest that different populations of misfolded A beta conformers compete to populate the brain.
Review
Cell Biology
Mario Gonzalez-Garcia, Giuliana Fusco, Alfonso De Simone
Summary: The conversion of soluble proteins into insoluble amyloid aggregates is linked to various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. The small prefibrillar oligomers formed during protein aggregation are identified as the most harmful species. Interactions with biological membranes play a crucial role in the onset of cellular toxicity. Further research is needed to understand the transient interactions involving heterogeneous protein aggregates for developing effective therapeutic strategies against protein misfolding diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Peter R. Christenson, Manci Li, Gage Rowden, Peter A. Larsen, Sang-Hyun Oh
Summary: Misfolded proteins associated with neurodegenerative diseases can accumulate in tissues or circulate in biological fluids before the onset of clinical symptoms, making them ideal diagnostic targets. Adding nanoparticles to the RT-QuIC assay improves its speed and sensitivity, which is crucial for diagnostic application.
Review
Chemistry, Multidisciplinary
Maksym Galkin, Anastasiia Priss, Yevhenii Kyriukha, Volodymyr Shvadchak
Summary: This article reviews small molecule, peptide, and protein inhibitors of alpha-synuclein fibrillization reported so far and discusses the specificity of inhibitors, their action mechanisms, and the strengths and weaknesses of different approaches to testing the inhibitors.
Review
Biochemistry & Molecular Biology
Diane L. Ritchie, Marcelo A. Barria
Summary: Accumulation and propagation of misfolded proteins in the brain are shared pathological features of many neurodegenerative diseases. While there is no epidemiological evidence suggesting infectiousness in neurodegenerative disorders, experimental models show potential prion-like transmission of other pathogenic proteins. Concerns exist regarding the transmission of misfolded proteins beyond prion protein.
Article
Cell Biology
Robert J. Shmookler Reis, Ramani Atluri, Meenakshisundaram Balasubramaniam, Jay Johnson, Akshatha Ganne, Srinivas Ayyadevara
Summary: The study found that neurodegenerative disease aggregates contain abundant nucleic acids, predominantly RNA, which map to specific genes along with non-protein constituents. RNA content is significantly increased in diseased tissues, similar to protein levels, and the nucleic acid mappings are notably nonrandom in nature.
Article
Chemistry, Medicinal
Xianwei Sun, Prasad Admane, Zbigniew A. Starosolski, Jason L. Eriksen, Ananth Annapragada, Eric A. Tanifum
Summary: The study focused on developing new imaging agents for in vivo detection of alpha-synuclein pathologies by designing and synthesizing novel derivatives. The results showed that two lead compounds exhibited high affinity and selectivity for alpha-syn fibrils, selectively labeling all forms of alpha-syn on PD brain tissue sections.
Article
Clinical Neurology
P. Codron, F. Letournel, S. Marty, L. Renaud, A. Bodin, M. Duchesne, C. Verny, G. Lenaers, C. Duyckaerts, J-P Julien, J. Cassereau, A. Chevrollier
Summary: This study used STORM super-resolution imaging technique to analyze human brain tissue samples, successfully imaging pathological aggregates in the central nervous system of patients with neurodegenerative diseases, providing a more comprehensive understanding of common neurological disorders.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Elisabeth Sanchez-Mejias, Cristina Nunez-Diaz, Raquel Sanchez-Varo, Angela Gomez-Arboledas, Juan Antonio Garcia-Leon, Juan Jose Fernandez-Valenzuela, Marina Mejias-Ortega, Laura Trujillo-Estrada, David Baglietto-Vargas, Ines Moreno-Gonzalez, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez
Review
Biochemistry & Molecular Biology
Karina Cuanalo-Contreras, Ines Moreno-Gonzalez
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Maritza Onate, Alejandra Catenaccio, Natalia Salvadores, Cristian Saquel, Alexis Martinez, Ines Moreno-Gonzalez, Nazaret Gamez, Paulina Soto, Claudio Soto, Claudio Hetz, Felipe A. Court
CELL DEATH AND DIFFERENTIATION
(2020)
Correction
Biochemistry & Molecular Biology
Maritza Onate, Alejandra Catenaccio, Natalia Salvadores, Cristian Saquel, Alexis Martinez, Ines Moreno-Gonzalez, Nazaret Gamez, Paulina Soto, Claudio Soto, Claudio Hetz, Felipe A. Court
CELL DEATH AND DIFFERENTIATION
(2020)
Editorial Material
Geriatrics & Gerontology
Ines Moreno-Gonzalez, Rodrigo Morales, David Baglietto-Vargas, Raquel Sanchez-Varo
FRONTIERS IN AGING NEUROSCIENCE
(2020)
Article
Multidisciplinary Sciences
Juan Jose Fernandez-Valenzuela, Raquel Sanchez-Varo, Clara Munoz-Castro, Vanessa De Castro, Elisabeth Sanchez-Mejias, Victoria Navarroz, Sebastian Jimenez, Cristina Nunez-Diaz, Angela Gomez-Arboledas, Ines Moreno-Gonzalez, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Jean Wu, Colin Carlock, Junbo Shim, Ines Moreno-Gonzalez, William Glass, April Ross, Tatiana Barichello, Joao Quevedo, Yahuan Lou
Summary: IL33 is essential for regulating the expression of AQP4 in astrocytes, with its deficiency leading to abnormal tau accumulation in neurons and impaired drainage. This study suggests that different forms of AQP4 play distinct roles in glymphatic drainage, with p-AQP4 driving flow toward perivenous space while n-AQP4 may help remove neuronal wastes. Defects in IL33-related mechanisms may contribute to chronic neurodegeneration and tauopathy in aging mice.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Rodrigo Morales, Javiera Bravo-Alegria, Ines Moreno-Gonzalez, Claudia Duran-Aniotz, Nazaret Gamez, George Edwards, Claudio Soto
Summary: This study demonstrates that administration of Aβ seeds through various peripheral routes can accelerate the accumulation of Aβ in the brains of AD mouse models. Oral administration of brain extracts had no impact on brain pathology. The peripheral administration of Aβ seeds led to the generation of a large proportion of aggregates in blood vessels, suggesting a role of vascular transport in AD-related pathological changes.
MOLECULAR PSYCHIATRY
(2021)
Review
Clinical Neurology
Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nunez-Diaz, Jose Carlos Davila, Javier Vitorica, Frank M. LaFerla, Ines Moreno-Gonzalez, Antonia Gutierrez, David Baglietto-Vargas
Summary: Alzheimer's disease is an incurable neurodegenerative disease affecting over 45 million people worldwide, with transgenic mouse models playing a significant role in elucidating its pathogenic mechanisms. However, limitations of current animal models highlight the need for more reliable models and human cellular models to improve the success rate of translating preclinical therapies into human treatments.
Article
Neurosciences
Claudia Duran-Aniotz, Ines Moreno-Gonzalez, Nazaret Gamez, Nelson Perez-Urrutia, Laura Vegas-Gomez, Claudio Soto, Rodrigo Morales
Summary: Diverse patterns of misfolded protein deposition in Alzheimer's disease brains may lead to different phenotypes in recipient mice, suggesting that AD-subtypes are encoded in disease-associated amyloid-beta.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Carson E. Finger, Ines Moreno-Gonzalez, Antonia Gutierrez, Jose Felix Moruno-Manchon, Louise D. McCullough
Summary: Aging is closely associated with chronic systemic inflammation and the development of various age-related diseases, including vascular disease. Poor outcomes after stroke in aged patients are predicted due to altered immune response, which differs from that of younger patients.
MOLECULAR PSYCHIATRY
(2022)
Review
Cell Biology
Jade de Oliveira, Ewa Kucharska, Michelle Lima Garcez, Matheus Scarpatto Rodrigues, Joao Quevedo, Ines Moreno-Gonzalez, Josiane Budni
Summary: Alzheimer's disease is the leading cause of dementia worldwide, with the amyloid cascade hypothesis being the most recognized explanation for AD pathology. The mechanisms underlying late onset AD are not completely clear, with BBB disruption playing an essential role in neuroinflammation and AD development. Systemic inflammation triggered by conditions like metabolic diseases or infections may contribute to the neurodegeneration observed in AD.
Article
Medicine, General & Internal
Ines Moreno-Gonzalez, George A. Edwards, Omar Hasan, Nazaret Gamez, Jonathan E. Schulz, Juan Jose Fernandez-Valenzuela, Antonia Gutierrez, Claudio Soto, Paul E. Schulz
Summary: This study focused on validating the effectiveness of the PET tracer F-18-THK5351 in detecting early changes in tau-related pathology, showing increased PET signaling over time in transgenic P301S tau mice with positive correlations to histological and biochemical tau changes, as well as motor, memory, and learning impairment. The findings suggest that F-18-THK5351 could be a useful tool in diagnosing tauopathies, understanding their pathophysiologies, and monitoring treatment trials.
Review
Biochemistry & Molecular Biology
Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nunez-Diaz, Laura Caceres-Palomo, Laura Vegas-Gomez, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Ines Moreno-Gonzalez, Marisa Vizuete, Javier Vitorica, David Baglietto-Vargas, Antonia Gutierrez
Summary: This review provides an overview of the major pathological elements of Alzheimer's disease and discusses the insights provided by mouse models in understanding the underlying mechanisms. It highlights the pros and cons of current models and explores the potential benefits of combining transgenic mice with omics technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Akihiko Urayama, Ines Moreno-Gonzalez, Diego Morales-Scheihing, Vineetkumar Kharat, Sandra Pritzkow, Claudio Soto
Summary: Alzheimer's disease is the major form of dementia in the elderly, characterized by neuronal death, synaptic alterations, brain inflammation, and the presence of protein aggregates. Exchanging blood with normal mice can reduce amyloid plaques and improve spatial memory in AD mice, suggesting a potential peripheral target for AD therapy.
MOLECULAR PSYCHIATRY
(2022)