Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania Medical Center
Protein interactions demonstrate that Alzheimer’s and Parkinson’s
disease may share a common fiber
Tau and alpha-synuclein proteins encourage each other to produce brain
lesions
(Philadelphia, PA) – The amyloid lesions that cause Alzheimer’s and
Parkinson’s disease are made of clumps of tangled proteins, but these
clumps are composed of different protein subunits. Researchers at the
University of Pennsylvania School of Medicine have discovered, however,
that the tau proteins found in Alzheimer’s disease and the alpha
(?)-synuclein proteins found in Parkinson’s disease can facilitate each
other to form amyloid lesions in the laboratory.
Their findings, presented in this week’s issue of Science, provide
insights into the mechanisms underlying both diseases and suggest that
therapeutics developed for one disease might be efficacious for both.
“We are trying to understand the basic pathological overlap between the
different amyloid lesions that cause Alzheimer’s and Parkinson’s, ” said
Virginia M. -Y. Lee, PhD, professor in Penn’s Department of Pathology
and Laboratory Medicine and Director of Penn’s Center for
Neurodegenerative Disease Research (CNDR). “This fundamental
relationship may explain why patients with one disease are more likely
to exhibit signs of the other disease.”
The researchers showed that the ?-synuclein proteins that form Lewy
bodies in Parkinson’s disease can induce tau proteins to form the sort
of fiber aggregates found in Alzheimer’s disease. Moreover, interactions
between the tau and the ?-synuclein proteins can dramatically induce the
formation of fibrous clumps of both proteins.
“This newly uncovered interaction between these two proteins suggests
that therapeutic agents created to directly or indirectly inhibit the
formation of one form of amyloid lesion might be effective for treating
other forms of amyloid lesions,” said Benoit Gaisson, PhD, lead author
of the paper and researcher at the CNDR. “That is, a drug meant to keep
Lewy bodies from forming to prevent Parkinson’s disease might also help
prevent tau tangles from forming in Alzheimer’s disease.”
The two proteins, tau and ?-synuclein are naturally abundant in the
brain, but have distinct functions. Tau has a binding role in the
structures of neurons, while ?-synuclein is thought to be involved in
regulating communications in the synapses between neurons.
The researchers knew that the smaller of the two proteins, ?-synuclein,
could bind to itself in homogenous clumps. The tau protein, meanwhile,
is larger and it requires co-factors to aid overcoming a folding
threshold. While the Penn researchers initially demonstrated that
?-synuclein could aid tau into forming fibers in a test tube, the
researchers also wanted to know if this also occurred in vivo. Using
mouse models, they were able to demonstrate that ?-synuclein
polymerization alone is sufficient to induce the assembly of tau clumps
in cells of the brain. Moreover, they were able to demonstrate that the
same phenomenon occurs in a similar group of individuals with a known
genetic abnormality in the ?-synuclein gene.
“After this initial step, we see a cycle begin to emerge,” said Gaisson.
“Tau and ?-synuclein work together to promote and propagate each other’s
formation of fibrous clumps and, hence, the amyloid lesions that cause
disease.”
###
Other scientists involved in the research paper described here include
Mark S. Forman, Makoto Huguchi, Charles L. Graves, Paul T. Kotzbauer,
and John Q. Trojanowski from Penn; and Lawrence I. Golbe from the
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson
Medical School.
Funding for this research was supported by the National Institutes on
Aging and by a Pioneer Award from the Alzheimer’s Association.
-- Kathrynne Holden, MS, RD < fivestar@nutritionucanlivewith.com > "Ask the Parkinson Dietitian" http://www.parkinson.org/ "Eat well, stay well with Parkinson's disease" "Parkinson's disease: Guidelines for Medical Nutrition Therapy" http://www.nutritionucanlivewith.com/
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