Newly Discovered Protein TAF15 Linked to Premature Dementia, Revealed Through Cryogenic Electron Microscopy
Researchers at the Medical Research Council (MRC) Laboratory of Molecular Biology at the University of Cambridge in the UK have unveiled groundbreaking findings regarding the molecular basis of frontotemporal dementia. This type of dementia, which presents earlier than Alzheimer’s disease, has long been a subject of study, and the latest research has shed light on a previously unidentified protein, TAF15, as a potential cause.
The study, led by Dr. Benjamin Riskeldi-Falcon, has revealed that TAF15 aggregates in the brain may be a key contributor to frontotemporal dementia, a degenerative condition affecting the frontal and temporal lobes of the brain. Unlike Alzheimer’s disease, which mainly affects older individuals, frontotemporal dementia tends to manifest in individuals between the ages of 45 and 65, and the discovery of TAF15’s role could lead to new diagnostic and treatment approaches for this condition.
Using advanced cryo-electron microscopy (cryo-EM), the research team analyzed the brain tissue of patients with frontotemporal dementia, identifying the presence of TAF15 amyloid filaments. This unexpected finding challenges the existing understanding of neurodegenerative diseases and opens up new possibilities for targeted therapies.
Furthermore, the study revealed a potential link between TAF15 and motor neuron disease, a condition characterized by progressive muscle loss. This connection suggests that TAF15 may play a role in multiple neurodegenerative conditions, leading to further avenues of exploration in the field of dementia research.
The use of cryo-EM in this study represents a significant technological advancement, providing insights that were previously unattainable. Dr. Stephen Teter, the study’s first author, highlighted the essential role of cryogenic electron microscopy in expanding our understanding of the molecular pathology of dementia and neurodegenerative diseases.
The discovery of TAF15’s involvement in frontotemporal dementia and its potential link to motor neuron disease has been published in the prestigious journal Nature, marking a significant contribution to the scientific community’s understanding of these complex conditions.
University of Cambridge: “Premature dementia is linked to the TAF15 protein, not the FUS protein”… Discovered thanks to cryogenic electron microscopy
Entered 2023.12.07 11:10 Views 2 Entered 2023.12.07 11:10 Modified 2023.12.07 09:29 Views 2
Structure of TAF15 amyloid filaments collected from the brain of a patient with frontotemporal dementia. Yellow is a TAF15 protein. This was analyzed using cryogenic electron microscopy (cryo-EM). [사진=케임브리지대 제공(S. Tetter/MRC Laboratory of Molecular Biology)]Research results have revealed that a new protein involved in ‘frontotemporal dementia’, a type of dementia that appears earlier than Alzheimer’s disease, has been discovered.
The Medical Research Council (MRC) Laboratory of Molecular Biology (MRC) at the University of Cambridge, UK, has correctly identified a malignant protein (TAF15) and its aggregated structure that had not been identified as a cause of antepartum dementia (approx. 5-). 10% of dementia).
Most neurodegenerative diseases, including dementia, are associated with proteins that aggregate into filaments called amyloid. In particular, Alzheimer’s disease, which accounts for the majority of dementias (50-80%), is caused by the accumulation and aggregation of amyloid-beta protein and tau protein.
Frontotemporal dementia is caused by degeneration of the frontal and temporal lobes of the brain, which control emotions, personality, behavior, language, and understanding words. It tends to start at a younger age than Alzheimer’s disease. It is often diagnosed between the ages of 45 and 65, but it can also affect younger or older people.
“This discovery greatly advances our understanding of the molecular basis of frontotemporal dementia,” said Dr Benjamin Riskeldi-Falcon, who led the study. “We discovered a new component of a small group of proteins known to aggregate in neurodegenerative diseases.” It is now possible to target these conjugated proteins for diagnostic testing and treatment of dementia.
The research team analyzed protein aggregates from the donated brains of four patients with frontotemporal dementia using state-of-the-art cryo-electron microscopy (cryo-EM). The research team confirmed that protein aggregates in all brains have the same atomic structure. Unexpectedly, the protein was not ‘FUS’ but a different protein called ‘TAF15’.
Some patients with frontotemporal dementia also suffer from motor neuron disease, which causes them to gradually lose control of their muscles. The research team revealed that two out of four people suffer from this disease and identified aggregated structures identical to TAF15 in their brains. The presence of the same TAF15 aggregate in two people showing signs of frontotemporal dementia and motor neuron disease means that the TAF15 protein may be the cause of both diseases.
“TAF15 was not known to form amyloid filaments in neurodegenerative diseases, and the protein structure did not exist,” said Dr. Stephen Teter, first author of the study. Therefore, the results of this study are unexpected.”
He emphasized, “Cryo-EM, an ultra-low temperature electron microscope that analyzes protein structures, plays a major role in expanding our understanding of the molecular pathology of dementia and neurodegenerative diseases by providing insight beyond the capabilities of previous technologies.” Dr. received Richard Henderson, a biologist at the University of Cambridge in England, the 2017 Nobel Prize in Chemistry for his breakthroughs in cryogenic electron microscopy.
The research team is studying whether abnormally aggregated TAF15 exists in patients with motor neuron disease without frontoperipheral dementia. The results of this study (TAF 15 amyloid filaments in fronto-medial lobar degeneration) were published in the international journal Nature.
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