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Tips from the American Journal of Pathology
Date:3/24/2009

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Alzheimer's disease is an incurable, degenerative, terminal form of dementia, thought to be caused in part by the presence of "tangles" of misfolded proteins. The unfolded protein response protects cells from the toxic effects of accumulated misfolded proteins; however, prolonged activation of the unfolded protein response, such as in Alzheimer's disease, may lead to cell death.

Hoozemans et al hypothesized that the unfolded protein response contributed to neurodegeneration in Alzheimer's disease partially though its effects on the accumulation of hyperphosphorylated tau, a major component of tangles in Alzheimer's disease patients. They found that markers of the unfolded protein response were expressed in areas of tau accumulation in patients with Alzheimer's disease. These unfolded protein response-related proteins were expressed early, in pre-tangle neurons, but were absent in tangle neurons.

This report suggests that "unfolded protein response activation occurs at an early stage of neurofibrillary degeneration and that the prolonged activation of the [unfolded protein response] is involved in both tau phosphorylation and neurodegeration in [Alzheimer's Disease] pathogenesis. Future studies will address the therapeutic opportunities of this pathway for the treatment of [Alzheimer's Disease] and other tauopathies."

Hoozemans JJM, van Haastert ES, Nijholt DAT, Rozemuller AJM, Eikelenboom P, Scheper W: The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. Am J Pathol 2009, 174: 1241-1251


Bacterial Toxin Leads to Systemic Infection

A group led by Dr. Michael Klapproth at Emory University, Atlanta suggests that bacterial lymphotoxin disrupts intestinal epithelial barrier function. They report these findings in the April 2009 issue of The American Journal of Pathology.

Numerous bacterial species commonly live in the human
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Contact: Angela Colmone
acolmone@asip.org
301-634-7953
American Journal of Pathology
Source:Eurekalert

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