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
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.
Article
Neurosciences
Giada Lavigna, Antonio Masone, Ihssane Bouybayoune, Ilaria Bertani, Jacopo Lucchetti, Marco Gobbi, Luca Porcu, Stefano Zordan, Mara Rigamonti, Luca Imeri, Elena Restelli, Roberto Chiesa
Summary: Doxycycline shows some therapeutic effects in the FFI mouse model, improving cognitive impairment and motor symptoms associated with sleep dysfunction, but it does not prevent the onset and progression of the disease, nor does it change the amount of aggregated protein or microglial activation.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Anastasiia A. Stepanchuk, Megan L. Morgan, Jeffrey T. Joseph, Peter K. Stys
Summary: Protein misfolding is a prominent feature of neurodegenerative disorders like Alzheimer's disease. A study investigated the binding affinity of fluorescent amyloid probes BSB and MCAAD to disease-related protein aggregates, and analyzed mouse and human brain samples using these probes and quantitative spectral phasor analysis. The approach revealed heterogeneity of protein aggregates across the samples and detected spectral differences between cognitively normal and AD cases, suggesting widespread proteopathy associated with the disease. This method offers a more sensitive, objective, and quantitative examination of protein misfolding pathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Zhiyu Wang, Yanfei Wang, Jagadeesh Prasad Pasangulapati, Kurt R. Stover, Xiaojing Liu, Stephanie (Wohnig) Schier, Donald F. Weaver
Summary: This study reports a series of furosemide analogs that target both A beta aggregation and neuroinflammation, addressing the combined proteopathic-immunopathic pathogenesis of Alzheimer's disease. These compounds demonstrate dual activity against A beta aggregation and neuroinflammation, suggesting potential therapeutic utility against Alzheimer's disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Patricia Aguilar-Calvo, Alejandro M. Sevillano, Suhail Rasool, Kevin J. Cao, Lyndsay M. Randolph, Robert A. Rissman, Stella T. Sarraf, Jerry Yang, Christina J. Sigurdson
Summary: The retina can be used to diagnose and monitor neurodegenerative diseases, and live imaging using an amyloid-binding fluorescent probe and high-resolution retinal microscopy can directly monitor the progression of amyloid deposits in the eyes.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Multidisciplinary Sciences
Maximo Sanz-Hernandez, Joseph D. Barritt, Jens Sobek, Simone Hornemann, Adriano Aguzzi, Alfonso De Simone
Summary: The T183A variant of human PrP significantly enhances aggregation propensity, leading to amyloid formation under physiological conditions by the sole C-terminal domain of the protein. The study identified the structural characteristics of the misfolded intermediate promoting aggregation of T183A huPrP and the interactions preventing the population of this species in the wild-type protein, supporting the use of POM antibodies to suppress the aggregation of this amyloidogenic mutant.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Jiang Chen, Anran Fan, Song Li, Yan Xiao, Yanlin Fu, Jun-Sheng Chen, Dan Zi, Ling-Hui Zeng, Jun Tan
Summary: Alzheimer's disease (AD), the most common type of dementia, is characterized by the presence of extracellular senile plaques composed of beta-amyloid peptides and intracellular neurofibrillary tangles containing phosphorylated-tau protein. This study has demonstrated the interaction between soluble tau and the N-terminal of amyloid precursor protein (APP) in vitro and in vivo, as well as the involvement of APP in the cellular uptake of tau through endocytosis. Targeting the pathological interaction between N-terminal APP and tau could be a promising therapeutic strategy for AD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nilamuni H. de Silva, Suneela Pyreddy, Ewan W. Blanch, Helmut M. Hugel, Subashani Maniam
Summary: A library of Sox-pyrrolizidines was efficiently synthesized through a new method, and Nitro-Sox compounds were found to inhibit HEWL amyloid fibril formation. Further experiments suggested that these compounds could potentially combat amyloid misfolding, indicating their potential for Alzheimer's disease treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Harshitha Santhosh Kumar, James Moore, Adrian C. Steiner, Emmanuel Sotirakis, Benjamin Schaerli, Patricia Isnard-Petit, Kader Thiam, David P. Wolfer, Erik C. Boettger
Summary: This study investigates the role of protein homeostasis in the accumulation of Alzheimer's associated protein A beta and levels of associated Tau phosphorylation. Surprisingly, disruptions in protein homeostasis did not significantly affect A beta accumulation and phosphorylated Tau levels.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Geriatrics & Gerontology
Ines Moreno-Gonzalez, George Edwards, Rodrigo Morales, Claudia Duran-Aniotz, Gabriel Escobedo Jr, Mercedes Marquez, Marti Pumarola, Claudio Soto
Summary: Alzheimer's disease (AD) is one of the leading causes of dementia in late life, and the misfolding and aggregation of amyloid beta (A β) and tau proteins are thought to be hallmark events. Recent studies have shown that small quantities of preformed aggregates can induce protein misfolding and aggregation, similar to the transmission of prion diseases. This study investigated the presence of A β aggregates in the brains of aged cattle and their ability to promote AD pathological features. The findings demonstrate that cows can develop seeding-competent A β aggregates, similar to what is observed in AD patients.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Yijing Tang, Dong Zhang, Xiong Gong, Jie Zheng
Summary: This article primarily discusses and summarizes the mechanistic causes of Alzheimer's disease (AD). Different mechanisms of AD could potentially work together to initiate, trigger, and promote the onset and development of the disease. Some of these mechanisms are also applicable to other amyloid diseases, explaining the pathogenesis and pathology spreading among these diseases.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Neurosciences
Anastasiia A. Stepanchuk, Philip A. Barber, Tammaryn Lashley, Jeffrey T. Joseph, Peter K. Stys
Summary: The study demonstrates that specific spectral signatures correlated with different protein aggregates formed by different proteins can be detected using fluorescent amyloid probes and spectral confocal microscopy. The combination of spectral imaging and advanced image analysis tools allows for the detection of variability of protein deposits across different samples.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Kaori Tsukakoshi, Rikako Kubo, Kazunori Ikebukuro
Summary: In this study, a fusion protein called PrP-ALP was developed as a sensing element to detect toxic A beta oligomers. PrP-ALP showed strong affinity towards high molecular weight oligomers and has potential for detecting A beta oligomers. This study is important for understanding the pathogenesis of Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christopher Sun, Leah Slade, Prisca Mbonu, Hunter Ordner, Connor Mitchell, Matthew Mitchell, Fu-Cheng Liang
Summary: This study investigates the effect of a novel protein chaperone, cpSRP43, on Aβ aggregation. The results show that cpSRP43 can effectively prevent and reverse Aβ aggregation, keeping Aβ in the soluble monomeric form. This research may provide new insights for the treatment of Alzheimer's disease.
Article
Neurosciences
Sunkuk Kwon, Ines Moreno-Gonzalez, Kathleen Taylor-Presse, George Edwards, Nazaret Gamez, Olivia Calderon, Banghe Zhu, Fred Christian Velasquez, Claudio Soto, Eva M. Sevick-Muraca
JOURNAL OF ALZHEIMERS DISEASE
(2019)
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
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)