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- Posted Thursday May 26, 2011
TGen study identifies compounds that could slow down Alzheimer's disease
Naturally occurring plant alkaloids could fend off potential
loss of memory
PHOENIX, Ariz. - May 26, 2011 - A family of naturally occurring
plant compounds could help prevent or delay memory loss associated
with Alzheimer's disease, according to a new study by the
Translational Genomics Research Institute (TGen).
Beta-carboline alkaloids could potentially be used in therapeutic
drugs to stop, or at least slow down, the progressively
debilitating effects of Alzheimer's, according to the study
published recently in the scientific journal Public Library of
Science (PLoS) One.
One of these alkaloids, called harmine, inhibits a protein known as
DYRK1A, which has been implicated by this and other studies in the
formation tau phosphorylation. This process dismantles the
connections between brain cells, or neurons, and has been linked in
past TGen studies to Alzheimer's disease.
Tau is a protein critical to the formation of the microtubule
bridges in neurons. These bridges support the synaptic connections
that, like computer circuits, allow brain cells to communicate with
each other.
"Pharmacological inhibition of DYRK1A through the use of
beta-carboline alkaloids may provide an opportunity to intervene
therapeutically to alter the onset or progression of tau pathology
in Alzheimer's disease," said Dr. Travis Dunckley, Head of TGen's
Neurodegenerative Research Unit, and the study's senior
author.
Beta-carboline alkaloids are found in a number of medicinal plants.
They have antioxidant properties, and have been shown to protect
brain cells from excessive stimulation of neurotransmitters.
"(They) are natural occurring compounds in some plant species that
affect multiple central nervous system targets," the study
said.
Under normal circumstances, proteins regulate tau by adding
phosphates. This process of tau phosphorylation enables connections
between brain cells to unbind and bind again, allowing neurons to
connect and reconnect with other brain cells. However, this process
can go awry, allowing the formation of neurofibrillary tangles, one
of the signature indicators of Alzheimer's.
In this study, laboratory tests showed that harmine, and several
other beta-carboline alkaloids, "potently reduced'' the expression
of three forms of phosphorylated tau, and inhibited the ability of
DYRK1A to phosphorylate tau protein at multiple genetic sites
associated with tau pathology.
"These results suggest that this class of compounds warrant further
investigation as candidate tau-based therapeutics to alter the
onset or progression of tau dysfunction and pathology in
Alzheimer's disease," Dr. Dunckley said.
The Arizona Alzheimer's Consortium, the National Institute on
Aging, and the Louis Charitable Trust funded the study. The
Consortium is funded in part by the Arizona Legislature through the
Arizona Department of Health Services, which supported a portion of
the study. Members of the Consortium also participated in the
study. MediProPharma Inc. supported portions of the study.
PLoS is a non-profit organization of scientists and physicians
committed to making the world's scientific and medical literature a
freely available public resource.
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About the Arizona Alzheimer's Consortium
The Arizona Alzheimer's Consortium is a 501(c)(3) organization that
includes the state-supported Arizona Alzheimer's Research Center
(AARC), the National Institute on Aging (NIA)-funded Arizona
Disease Core Center (Arizona ADCC), and independently funded
research programs. Its seven member institutions include: Arizona
State University, Barrow Neurological Institute, Mayo Clinic
Arizona, Banner Sun Health Research Institute, the Translational
Genomics Research Institute (TGen), the University of Arizona, and
Banner Alzheimer's Institute. Its three affiliated institutions
include Banner Good Samaritan Medical Center, the Southern Arizona
Veterans Administration Health Care System and the University
Physician's Hospital at Kino. For more information, including the
consortium's upcoming scientific conference, go to:
www.azalz.org.
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
