Increasing brain enzyme may slow Alzheimer’s disease progression

LOS ANGELES — Increasing puromycin-sensitive aminopeptidase, the most abundant brain peptidase in mammals, slowed the damaging accumulation of tau proteins that are toxic to nerve cells and eventually lead to the neurofibrillary tangles, a major pathological hallmark of Alzheimer’s disease and other forms of dementia, according to a study published online in the journal, Human Molecular Genetics.

Researchers found they could safely increase the puromycin-sensitive aminopeptidase, PSA/NPEPPS, by two to three times the usual amount in animal models, and it removed the tau proteins in the neurons. Removing the tau proteins restored neuronal density and slowed down disease progression. Researchers detected no abnormalities caused by the increase in PSA/NPEPPS, suggesting that elevating PSA/NPEPPS activity may be a viable approach to treat Alzheimer’s disease and other forms of dementia, known a tauopathies.

“Our research demonstrated that increasing the brain enzyme known as PSA/NPEPPS can effectively block the accumulation of tau protein that is toxic to nerve cells and slow down the progression of neural degeneration without unwanted side effects,” said Stanislav L. Karsten, PhD, the corresponding author for the study and a principal investigator at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). “These findings suggest that increasing this naturally occurring brain peptidase, PSA/NPEPPS, may be a feasible therapeutic approach to eliminate the accumulation of unwanted toxic proteins, such as tau, that cause the neural degeneration associated with the devastating effects of Alzheimer’s disease and other forms of dementia.”

Alzheimer’s disease affects 2 million to 4 million Americans, and their ranks are expected to grow to as many as 14 million by the middle of the 21st century as the population ages.

The potential for PSA/NPEPPS to protect neurons from degeneration was first reported in a 2006 issue of the journal, Neuron. At that time, researchers hypothesized that PSA/NPEPPS may be a natural mechanism for protecting neurons. Dr. Karsten, who was the lead author of the 2006 study, said the new study is the first to provide the data confirming the neuroprotective role of PSA/NPEPPS in mammals.

The research was supported by the UCLA Alzheimer’s Disease Research Center, the CurePSP Society, RGK Foundation, UCLA Older Americans Independence Center, Liu Young Investigator Award, Alzheimer’s Association, LA BioMed and NARSAD, the brain and behavior research fund. The research paper may be accessed at: http://hmg.oxfordjournals.org/content/early/2011/02/14/hmg.ddr065.full.pdf+html

Founded in 1952, LA BioMed is one of the country’s leading nonprofit independent biomedical research institutes. It has more than 150 principal researchers conducting studies into improved treatments and cures for cancer, inherited diseases, infectious diseases, illnesses caused by environmental factors and more. It also educates young scientists and provides community services, including immunization and childhood nutrition programs. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA and located on the campus of Harbor-UCLA Medical Center. For more information, please visit www.LABioMed.org