Enzyme key in preventing Alzheimer's onset

70652986 — Mon, 26 Mar 2007 07:10:50 -0400

A new discovery has found that Pin1, an enzyme previously shown to prevent the formation of the tangle-like lesions found in the brains of Alzheimer's disease patients, also plays a pivotal role in guarding against the development of amyloid peptide plaques, the second brain lesion that characterizes Alzheimer's.

These new findings, shown in an animal study, provide further evidence that Pin1 (prolyl isomerase) is essential to protect individuals from age-related neurodegeneration and for the first time establish a direct link between amyloid plaques and tau tangles, the two abnormal structures that are considered the pathological hallmarks of this devastating disease. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, the study appears in the March 23, 2006 issue of the journal Nature.

"A century ago, in 1906, the German doctor Alois Alzheimer first observed an abundance of these plaques and tangles in the brains of Alzheimer's patients," explains the study's senior author, Kun Ping Lu, MD, PhD, an investigator in the Division of Cancer Cell Biology at BIDMC and associate professor of medicine at Harvard Medical School.

"Throughout the years, intensive studies have been done to find out the causes of these two major lesions, but the exact relationship between the two has remained controversial and elusive," he adds. "Coupled with recent independent studies showing that genetic changes in the human Pin1 gene are associated with reduced Pin1 protein levels as well as an increased risk of Alzheimer's disease, these new results suggest that lack of sufficient Pin1 enzyme may be a key culprit in the onset of Alzheimer's disease."

Lu, together with Tony Hunter from the Salk Institute, first identified the Pin1 enzyme in 1995. Eight years later, in 2003, Lu and his colleagues demonstrated that Pin1 promoted dephosphorylation of tau, thereby 'detangling' the protein which had become knotted and overburdened with excess phosphate molecules. They also confirmed that when Pin1 was missing, neurons in the regions of the brain responsible for memory would collapse under the weight of the tau protein tangles, ultimately leading to age-dependent neurodegeneration.

In this new study, Lu and his coauthors hypothesized that Pin1 might be acting in a similar fashion to regulate APP (amyloid precursor protein) cleavage and amyloid beta production, thereby preventing the formation of plaques.

This study was funded in part by grants from the National Institutes of Health, the National Science Foundation and the Taiwan National Science Council.

Cell protein potently blocks enzyme linked to cancer

70652986 — Mon, 26 Mar 2007 05:17:47 -0400

The ends of chromosomes in normal cells eventually unravel, causing the cells to die. This does not happen in cancer cells, however. Cancer cells use an enzyme named telomerase to rebuild the chromosome ends, which are called telomeres, in essence making cancer cells immortal. Since the discovery of the link between telomerase and cancer, scientists have been hunting for ways to turn the enzyme off, in hopes that such a therapy could render cancer cells mortal. Now, two Harvard Medical School researchers, Xiao Zhen Zhou and Kun Ping Lu, have discovered the first protein that potently inhibits telomerase, suggesting a potential new cancer therapy and a genetic link between telomeres, cancer, and cell division. Their research was reported in the Nov. 2, 2001, issue of the journal Cell.

all Kun Ping Lu stories

Enzyme key in preventing Alzheimer's onset

Cell protein potently blocks enzyme linked to cancer