Insulin Is A Possible New Treatment For Alzheimer’s
February 3, 2009
Adapted from Northwestern University
A composite image of two neurons.
(Left) Red shows the attachment of ADDLs (toxic proteins that build up in persons with Alzheimer's disease) to a nerve cell; green indicates synapses, parts of nerve cells where memory formation begins. When ADDLs are attached, synapses are eliminated.
(Right) A nerve cell treated with insulin before being exposed to ADDLs. The cell is normal, with high levels of synapses (green) and almost no ADDLs (red) bound to it.
Source: Northwestern University
A Northwestern University-led research team reports that insulin, by shielding memory-forming synapses from harm, may slow or prevent the damage and memory loss caused by toxic proteins in Alzheimer's disease.
The findings, which provide additional new evidence that Alzheimer's could be due to a novel third form of diabetes, will be published online the week of February 2, 2009 by the Proceedings of the National Academy of Sciences (PNAS).
In a study of neurons taken from the hippocampus, one of the brain's crucial memory centers, the scientists treated cells with insulin and the insulin-sensitizing drug rosiglitazone, which has been used to treat type 2 diabetes. (Isolated hippocampal cells are used by scientists to study memory chemistry; the cells are susceptible to damage caused by ADDLs, toxic proteins that build up in persons with Alzheimer's disease.)
ADDLs (short for “amyloid beta-derived diffusible ligands) were discovered at Northwestern and are known to attack memory-forming synapses, the tiny regions where information flows from one brain cell to another.
After ADDL attaches to cells, synapses lose their capacity to respond to incoming information, resulting in memory loss.
The researchers discovered that damage to neurons exposed to ADDLs was blocked by insulin, which kept ADDLs from attaching to the cells. They also found that protection by low levels of insulin was enhanced by rosiglitazone.
The protective mechanism of insulin works through a series of steps by ultimately reducing the actual number of sites that ADDL binding sites, which in turn results in a marked reduction of ADDL attachment to synapses, the researchers report.
“Therapeutics designed to increase insulin sensitivity in the brain could provide new avenues for treating Alzheimer's disease,” said senior author William L. Klein, a professor of neurobiology and physiology in the Weinberg College of Arts and Sciences and a researcher in Northwestern's Cognitive Neurology and Alzheimer's Disease Center. “Sensitivity to insulin can decline with aging, which presents a novel risk factor for Alzheimer's disease. Our results demonstrate that bolstering insulin signaling can protect neurons from harm.”
“The discovery that anti-diabetic drugs shield synapses against ADDLs offers new hope for fighting memory loss in Alzheimer's disease,” said lead author Fernanda G. De Felice, a former visiting scientist in Klein's lab and an associate professor at the Federal University of Rio de Janeiro, Brazil.
“Recognizing that Alzheimer's disease is a type of brain diabetes points the way to novel discoveries that may finally result in disease-modifying treatments for this devastating disease,” adds Sergio T. Ferreira, another member of the research team and a professor of biochemistry in Rio de Janeiro.
This work was supported by the Alzheimer's Association, the BrightFocus Foundation, the National Institute on Aging, the Howard Hughes Medical Institute, the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil), Fundacao de Amparo à Pesquisa do Estado do Rio de Janeiro (Brazil) and the Human Frontier Science Program.
On behalf of its donors, the Alzheimer's Disease Research program of the BrightFocus Foundation, is proud have funded Dr. Klein for this very important work.
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