How renegade protein interrupts brain cell function in Alzheimer's
disease

Date:
July 28, 2020
Source:
NYU Langone Health / NYU School of Medicine
Summary:
Dozens of molecules may tangle up with rogue bundles of tau,
a protein that normally gives nerve fibers structure, to cause
brain cell damage that contributes to neurodegenerative diseases,
a new study shows.



FULL STORY ========================================================================== Dozens of molecules may tangle up with rogue bundles of tau, a protein
that normally gives nerve fibers structure, to cause brain cell damage
that contributes to neurodegenerative diseases, a new study shows.


========================================================================== Neuroscientists have previously found that tau can become toxic when
extra chemical molecules accumulate with its structure in the brain,
causing it to form tangles of protein that destroy surrounding tissue.

Led by researchers from NYU Grossman School of Medicine, the new study
analyzed the makeup of such tangles and found 12 proteins that they say
have not before been tied to both tau and Alzheimer's disease. They also uncovered several dozen other proteins that appear in the latest stages
of the disease as well as in the earliest phases of dementia.

"Our findings expand our understanding of the molecular interactions that
drive Alzheimer's and other brain-damaging diseases related to misbehaving
tau proteins," says study co-lead author Eleanor Drummond, PhD, a research assistant professor in the Department of Neurology at NYU Langone Health.

"Now that we have better insight into possible 'key players' in neurodegeneration, we may have clearer targets for potential therapies,"
says co-lead author Geoffrey Pires, a doctoral student in neurology at
NYU Langone.

An estimated 5 million Americans are living with Alzheimer's, a
progressive disease that affects mostly those over 65 and interferes
with memory, language, and decision making. Currently, there are no
effective treatments or prevention strategies for Alzheimer's. Experts
have long linked it to a buildup of extra phosphate molecules on tau
proteins. However, how these tangles damage neurons and what other
proteins are involved in the development of Alzheimer's signature bundles
have been poorly understood, says Drummond.

The new study, publishing online July 28 in the journal Brain, provides
what Drummond and her colleagues say is the largest overview to date of proteins present in these tau tangles.

For the investigation, the research team analyzed donated brain tissue
samples from 12 men and women with Alzheimer's disease. After separating
the tau knots from the surrounding tissue, the researchers examined the
bundles to identify the many proteins tangled within.

According to the findings, the tangles were composed of 542 different
proteins in total, some of which are involved in essential processes
within cells, such as energy production (vacuolar-ATPase subunit
ATP6V0D1), the reading of genetic material (RNA binding protein HNRNPA1),
and cell breakdown and digestion (PSMC 1 through 5). These results
provide clues to how the tangles lead to neuron death, says Drummond.

"Alzheimer's has been studied for over a century, so it is eye opening
that we are still uncovering dozens of proteins that we had no idea are associated with the disease," says study senior author Thomas Wisniewski,
MD, the Gerald J. and Dorothy R. Friedman Professor in the Department
of Neurology at NYU Langone.

Wisniewski, also a professor in the departments of Pathology and
Psychiatry at NYU Langone, plans next to investigate the newly
identified proteins in tissue samples of people with other tau-linked neurodegenerative diseases, such as Pick's disease and chronic traumatic encephalopathy, as well as other forms of dementia.

Funding for the study was provided by National Institutes of Health
grants P01AG060882, P30AG066512, RF1 AG058267, and 1S10OD010582-01A1,
as well as the Bluesand Foundation and Dementia Australia.


========================================================================== Story Source: Materials provided by NYU_Langone_Health_/_NYU_School_of_Medicine. Note: Content may be edited
for style and length.


==========================================================================


Link to news story: https://www.sciencedaily.com/releases/2020/07/200728113601.htm

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