2008 Grant - Karsten

Neuroprotective Role of Puromycin-Sensitive Aminopeptidase

Stanislav L. Karsten, Ph.D.
Los Angeles Biomedical Research Institute at Harbor- UCLA Medical Center
Torrance, California

2008 New Investigator Research Grant

The protein tau is important for maintaining cell structure, but it is also the main component of neurofibrillary tangles, a characteristic feature of Alzheimer pathology. Because of this central role in Alzheimer's disease, researchers have been studying the function of tau and searching for enzymes that remove excess or abnormal tau.

Stanislav L. Karsten, Ph.D., and colleagues have identified a protein, puromycin-sensitive aminopeptidase (PSA), which shows evidence of being involved in the removal of tau from cells. Using genetically modified animal models, in which the expression of tau is increased, they have also found evidence that PSA reduced tau-dependent neurodegeneration. Furthermore, genetic manipulations that prevented the function of PSA led to worsening of neurodegeneration. These effects corresponded to decreases or increases, respectively, of tau levels in the brain.

Dr. Karsten and colleagues plan to continue their studies by examining the functional roles of PSA in mice. Using genetic engineering techniques, they have created mice that express large amounts of PSA. They plan to cross these mice with other genetically altered mice that express aspects of Alzheimer pathology, such as neurofibrillary tangles or amyloid plaques. The researchers will use a variety of techniques to monitor the onset and progression of neurodegeneration in these animal models.

These studies may reveal the role of PSA in removing excess or abnormal tau and may demonstrate the potential of increasing PSA as a therapeutic strategy for Alzheimer's disease.