[PHNUTR-L] Insulin receptor stops progression of Alzheimer's disease
Kathrynne Holden, MS, RD
fivestar at nutritionucanlivewith.com
Fri Sep 22 08:29:30 PDT 2006
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Public release date: 21-Sep-2006
Contact: Nicole Gustin
ngustin at lifespan.org
Insulin receptor stops progression of Alzheimer's disease
Patients could be treated in early phases of disease
Providence, RI – Stimulation of a receptor in the brain that controls
insulin responses has been shown to halt or diminish the
neurodegeneration of Alzheimer's disease, providing evidence that the
disease can be treated in its early stages, according to a study by
researchers at Rhode Island Hospital and Brown Medical School.
Researchers have found that peroxisome-proliferator activated receptor
(PPAR) agonists prevent several components of neurodegeneration and
preserve learning and memory in rats with induced Alzheimer's disease
(AD). They found that an agonist for PPAR delta, a receptor that is
abundant in the brain, had the most overall benefit.
"This raises the possibility that you can treat patients with mild
cognitive impairment who have possible or probable Alzheimer's disease.
This is really amazing because right now, there's just no treatment that
works," says lead author Suzanne M. de la Monte, MD, MPH, a
neuropathologist at Rhode Island Hospital and a professor of pathology
and clinical neuroscience at Brown Medical School in Providence, RI.
The study appears in the September issue (Volume 10, Issue 1) of the
Journal of Alzheimer's Disease (www.j-alz.com).
In previous studies, the researchers demonstrated that Alzheimer's is a
brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct
from other types of diabetes. They showed that insulin and IGF-I
receptors are produced separately in the brain, and begin to disappear
early in Alzheimer's and continue to decline as the disease progresses.
As insulin signaling breaks down, it leads to increased oxidative
stress, impaired metabolism and cell death – all causing neurodegeneration.
Scientists were also previously able to replicate Alzheimer's in rats
with Streptozotocin (STZ), a compound that is known to destroy insulin
producing cells in the pancreas and cause diabetes. When injected into
the brains of rats, the compound mimicked the neurodegeneration of
Alzheimer's disease – plaque deposits, neurofibrillary tangles,
diminished brain size, impaired cognitive function, cell loss and
overall brain deterioration.
Having created an animal model for Alzheimer's, researchers in this
study induced Alzheimer's with STZ and then administered treatment with
three classes of PPAR agonists – alpha, gamma and delta. All are found
in various tissues and organs in the body, including the brain, and PPAR
gamma is already FDA approved as a treatment for Type 2 diabetes, or
adult-onset diabetes. The two other classes of PPAR agonists have not
yet been approved for clinical use.
Following treatment, many of the abnormalities associated with
Alzheimer's were reduced or nearly disappeared. The agonists affected
different regions of the brain, with PPAR delta producing the most
striking effect in preserving the hypothalamus and temporal lobes, areas
of the brain responsible for memory, learning, and behavior. In these
brain regions, PPAR alpha and PPAR gamma were effective in reducing
amyloid gene expression. PPAR delta had the most benefit for reducing
oxidative stress and improving learning and memory.
"That was the most spectacular," de la Monte says, "because everybody
wants something for cognitive impairment, and that was the most improved
with the PPAR delta agonist."
Researchers were not able to stop the deterioration of insulin and its
receptors. However, by administering PPAR, they were able to bypass the
defects in insulin signaling and preserve the cells that need insulin to
thrive. PPAR molecules go directly to the nucleus of cells and tell DNA
to turn on or off genes that are normally regulated by insulin, thus
preventing them from dying and allowing them to communicate with each
other. The major effects of the PPAR treatments were to increase brain
size, preserve insulin and IGF-II receptor bearing neurons, and preserve
learning and memory.
"The trigger for dementia is the loss of insulin and IGF producing
cells. The cells that need those growth factors subsequently die. This
study shows you can block the second phase, which is responsible for
dementia. This is great news for patients since you treat early stages
of disease," de la Monte says.
Another promising result for Alzheimer's patients is that these drugs
could be given in the form of a pill, de la Monte says. In the study,
the drugs were injected to control the amounts administered.
"One of the most exciting findings was that peripheral (intraperitoneal)
injection of the PPAR agonists either partially or completely rescued
the brains from neurodegeneration," the authors write.
Alzheimer's appears to be caused by parallel abnormalities – impaired
insulin signaling and oxidative stress, which is regulated by the genes
NOS and NOX. The PPAR agonists treatments target both problems. They
preserve the cells regulated by insulin and IGF, and they decrease
oxidative stress, resulting in fewer lesions in the brain.
"If the diagnosis is suspected or patients are in the early phases of
AD, there's a good possibility they could get treatment that will help
them. It's possible that in the moderate phase, treatment will also
help, but more work needs to be done to show that," de la Monte says.
Treatment is not likely to work in the late stages of the disease, she
says, because the cells have already died.
Kathrynne Holden, MS, RD < fivestar at 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"
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