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
Neurosciences
Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni, Wen-Quan Zou
Summary: The study provided evidence that CWD PrPSc can cross the species barrier to convert human PrP(C) into infectious PrPSc, leading to clinical prion disease in humanized transgenic mice.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
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
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
Chemistry, Multidisciplinary
Yuanzi Sun, Kezia Jack, Tiziana Ercolani, Daljit Sangar, Laszlo Hosszu, John Collinge, Jan Bieschke
Summary: In prion diseases, the misfolded prion protein (PrP) can self-propagate through the incorporation of PrP monomers. This study reveals that PrP fibrils exist as a population of competing conformers and can mutate during elongation, similar to the concept of quasispecies in genetic organisms. The discovery of polymorphic fibril populations growing in competition suggests that prions and other amyloid-replicating structures can evolve to adapt to new hosts, making therapeutic intervention more challenging.
Article
Chemistry, Multidisciplinary
Yuanzi Sun, Kezia Jack, Tiziana Ercolani, Daljit Sangar, Laszlo Hosszu, John Collinge, Jan Bieschke
Summary: This study reveals that competing conformers of PrP fibrils exist in prion diseases, and they undergo selective amplification and mutation during elongation. This suggests that prion replication possesses molecular evolution steps similar to genetic organisms.
Review
Biochemistry & Molecular Biology
Sarah Vascellari, Aldo Manzin
Summary: This review discusses the shared pathological mechanism between Parkinson's disease and other neurological disorders, mainly related to the aggregation of alpha-synuclein, which progresses in a prion-like manner in the host.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Biochemistry & Molecular Biology
Roberta Cascella, Alessandra Bigi, Nunilo Cremades, Cristina Cecchi
Summary: Protein misfolding is a common feature of protein deposition diseases, and soluble oligomeric species may be more toxic than fibrillar forms. Recent research shows that the beta-sheet core of aSyn fibrils cannot establish persistent interactions with lipid bilayers, but can release oligomeric species that cause immediate dysfunction. These oligomeric species can also contribute to pathogenesis through neuron-to-neuron spreading.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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
Cell Biology
Chae Kim, Tracy Haldiman, Sang-Gyun Kang, Lenka Hromadkova, Zhuang Zhuang Han, Wei Chen, Frances Lissemore, Alan Lerner, Rohan de Silva, Mark L. Cohen, David Westaway, Jiri G. Safar
Summary: This study suggests that the variability in Alzheimer's disease progression could be attributed to different structural assemblies of TAU protein. Specifically, the rapidly replicating, misfolded TAU conformers found in rapidly progressive AD may drive the rapid decline in the disease. This finding implies that effective therapeutic strategies for AD might need to consider the diverse misfolded TAU conformers rather than a singular species.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
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
Biochemistry & Molecular Biology
Li-Qiang Wang, Han-Ye Yuan, Jing Tao, Miao-Miao Hao, Jie Chen, Hai-Li Zhu, Yi Liang
Summary: Human PrP fibrils exhibit cytotoxicity and can induce misfolding of endogenous PrPC in both cells and frontal cortices of infant mice. The fibrils also cause severe mitochondrial damage, increase ROS production, and induce late apoptosis in cells expressing PrPC.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Christina Kelly, Yusef Ahmed, Omar Elghawy, Nikole Fandino Pachon, Matthew S. Fontanese, Seongchan Kim, Erica Kitterman, Amanda Marley, Danielle Terrenzio, Richard Wike, Theodora Zeibekis, Dale M. Cameron
Summary: Understanding the mechanisms cells employ to ensure the integrity of the proteome is crucial in developing potential therapeutic interventions for human diseases associated with misfolding of amyloidogenic proteins. Yeast cells possess prion-forming proteins capable of adopting amyloid conformations, and the ribosome-associated complex (RAC) can moderate the acquisition of these conformations in yeast. The study found that the human RAC can partially correct the growth defect and reduce conversion to a prion conformation in yeast lacking endogenous RAC, but is unable to counter the toxicity from expression of a pathogenically expanded polyQ protein.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Keiji Uchiyama, Hideyuki Hara, Junji Chida, Agriani Dini Pasiana, Morikazu Imamura, Tsuyoshi Mori, Hanae Takatsuki, Ryuichiro Atarashi, Suehiro Sakaguchi
Summary: Advanced DMEM may contain anti-prion compounds that reduce PrPSc levels, with ethanolamine identified as having anti-prion activity. Oral administration of ethanolamine delayed the onset of prion disease in mice, suggesting it could be a new anti-prion compound.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)