Increasing brain enzyme may slow Alzheimer's disease progression

February 16, 2011
Stanislav Karsten, an LA BioMed principal researcher, is the lead author of a new study on Alzheimer's disease. Credit: LA BioMed

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 that is toxic to 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.

Explore further: Untangling a pathology of Alzheimer's

More information: The research paper may be accessed at hmg.oxfordjournals.org/content/early/2011/02/14/hmg.ddr065.full.pdf+html

Related Stories

Untangling a pathology of Alzheimer's

September 6, 2006

Researchers have uncovered what appears to be a natural protective mechanism against a central cause of neuronal death in Alzheimer's and similar neurodegenerative diseases. They theorize that it may be possible to use drugs ...

Acetylation may contribute to dementia and Alzheimer's disease

September 22, 2010

A new study uncovers a protein modification that may contribute to the formation of neuron-damaging neurofibrillary tangles in the human brain. The research, published by Cell Press in the September 23 issue of the journal ...

Tau disrupts neural communication prior to neurodegeneration

December 22, 2010

A new study is unraveling the earliest events associated with neurodegenerative diseases characterized by abnormal accumulation of tau protein. The research, published by Cell Press in the December 22 issue of the journal ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.