Scientists have found a protein associated with frontotemporal dementia. Oriol Llauradó Ballesta/Stocksy
- Scientists
at the Medical Research Council (MRC) Laboratory of Molecular Biology in
Cambridge, UK, have identified
a novel protein called TAF15 forming aggregated structures in cases of
frontotemporal dementia, challenging previous assumptions about the
condition.
- This discovery is a novel addition to the
limited set of proteins recognized for aggregating in neurodegenerative
disorders like Alzheimer’s.
- This finding not only paves the way for
advanced diagnostic tools and treatments but also raises the intriguing
possibility that TAF15 may be linked to both frontotemporal dementia and
motor neuron disease, shedding new light on these debilitating disorders.
Most neurodegenerative disorders, such as dementia, involve proteins clustering into
filaments known as amyloids.
In most cases, scientists have pinpointed the proteins
responsible for this aggregation, enabling them to focus on these proteins for
diagnostic assessments and therapies.
However, in approximately 10% of frontotemporal dementia cases,
researchers had not yet determined the specific protein responsible.
Now,
researchers have successfully identified the aggregated structures of the TAF15
protein in these particular cases.
The findings were published in
Novel protein may contribute to frontotemporal
dementia
Frontotemporal dementia
arises from the deterioration of the brain’s frontal and temporal lobes, which
oversee emotions, personality, behavior, language comprehension and speech.
This
condition typically manifests at an earlier age compared to Alzheimer’s
disease, frequently being diagnosed in individuals between 45 and 65 years old.
However, it can also present in individuals both younger and older.
In their new research, a team of scientists uncovered
aggregated protein structures that may serve as a focal point for potential
advancements in diagnostic assessments and therapies.
With the identification of the key protein and its
structure, the researchers are now poised to focus on it to diagnose and treat
this specific form of frontotemporal dementia.
This approach mirrors the strategies already in
progress for targeting amyloid-beta and tau protein aggregates—hallmark
features of Alzheimer’s disease.
Utilizing advanced cryo-electron microscopy to examine the
brain
The scientists utilized advanced cryo-electron microscopy
(cryo-EM) techniques to examine protein aggregates at an atomic level
resolution in the brains of four individuals with this form of frontotemporal
dementia.
Until now, scientists had assumed that a protein named
FUS was responsible for aggregation in this type of dementia, drawing parallels
with other neurodegenerative disorders.
Utilizing cryo-electron microscopy (cryo-EM), the MRC
Laboratory of Molecular Biology scientists successfully determined that the
protein aggregates found in each brain shared an identical atomic structure.
Surprisingly, the responsible protein was not FUS but
another protein called TAF15.
The
researchers clarified that this outcome was unexpected, as prior to this study,
TAF15 had not been recognized for its role in forming amyloid filaments in
neurodegenerative conditions, and no information about its structural
characteristics existed.
Cryo-EM is revolutionizing our comprehension of the
molecular mechanisms underlying dementia and neurodegenerative diseases in a
broader context by providing insights that were previously unattainable with
earlier technologies.
The researchers acknowledged that the intricate nature
of conducting cryo-electron microscopy limited their examination to only four
individuals’ brains.
Nevertheless, with our newfound knowledge of the
pivotal protein and its structure, there is the prospect of creating tools for
screening hundreds of patient samples to assess the extent of these abnormal
protein aggregates.
Some individuals affected by frontotemporal dementia also
experience motor neuron disease, a condition characterized by a progressive
loss of muscle control.
In this investigation, two individuals who had both
conditions donated their brains for study.
In these cases, the researchers detected the same
aggregated form of the TAF15 protein in brain regions associated with motor
neuron disease.
The
presence of identical TAF15 aggregates in two individuals who had both
frontotemporal dementia and signs of motor neuron disease raises the
possibility that TAF15 may contribute to the development of both disorders.
Further
research needed to investigate the impact of TAF15
The research team is currently examining whether these
abnormal TAF15 aggregates are present in individuals with motor neuron disease
who do not exhibit symptoms of frontotemporal dementia.
James
Giordano, PhD, MPhil, Pellegrino Center Professor of Neurology and
Biochemistry at Georgetown University Medical Center, not involved in this
research, told Medical
News Today that “this study further examined the possibility that
additional abnormal proteins may be contributory to the neuropathological
process of fronto temporal lobar degeneration and dementia (FTLD).”
“The study was well
conducted and utilized a fairly broad sample of brain tissue taken from
affected patients to evaluate the presence and extent of TAF protein, a variant
abnormal protein constituent, which, together with other known abnormal
proteins (such as characteristic tau and alpha-synuclein entities), are found
in and contributory to the neurodegenerative processes of FTLD.”
— Dr. James Giordano
Dr. Giordano noted that “this study importantly,
demonstrated that TAF protein is also present, albeit in somewhat lesser
concentration, in the total proteinopathic constituency of the brains of these
patients.”
Dr. Giordano noted that the study findings “further
support and advance aspects of the amyloid hypothesis of neurodegenerative
dementia.”
“Further,
the identification of TAF variant may serve as an important diagnostic marker,
as well as a potential therapeutic target in the treatment of FTLD,” he
explained.
Jennifer Bramen,
Ph.D., senior research scientist at the Pacific Neuroscience Institute in Santa
Monica, CA, also not involved in this research,“frontotemporal lobe dementia
(FTD) is an emotionally challenging disease with no cure.”
Dr. Bramen concluded that “FTD is a heterogenous
disease, making it more challenging to research. A better understanding of
different subtypes could ultimately lead to more treatment options for
patients.”
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