Tag Archives: neuronal death

Asthma drug could treat dementia

Researchers at Temple University”s School of Medicine have found that a drug used to treat asthma can reduce the formation of amyloid beta, a peptide in the brain that is implicated in the development of Alzheimer”s disease.

In previous studies, the Temple researchers discovered that 5-lipoxygenase, an enzyme long known to exist in the brain, controls the activation state of gamma secretase, another enzyme that is necessary and responsible for the final production of amyloid beta. When produced in excess, amyloid beta causes neuronal death and forms plaques in the brain. The amount of these amyloid plaques in the brain is used as a measurement of the severity of Alzheimer”s.

Alzheimer's

Alzheimer's

In their current study, led by Domenico Pratico, an associate professor of pharmacology in Temple”s School of Medicine, the researchers tested the drug Zileuton, an inhibitor of 5-lipoxygenase typically used to treat asthma, in a transgenic mouse model of Alzheimer”s disease. At the end of the treatment they found that this drug, by blocking the 5-lipoxygenase, reduced gamma secretase”s production of amyloid beta and the subsequent build up of amyloid plaques in the brain by more than 50 percent.


Pratico said that gamma secretase is present throughout the body and, despite its role in the development of amyloid plaques, plays a significant role in numerous important functions. Direct inhibitors of gamma secretase are known, he said, but blocking the enzyme completely may cause problems such as the development of cancer. Unlike classical gamma secretase inhibitors, Zileuton only modulates the protein expression levels, which keeps some of its vital functions in tact while blocking many of its bad effects, which in this case is the development of the amyloid plaques.

The findings have been published in the American Journal of Pathology.

Alzheimer’s and Parkinson’s update

Scientists have identified a potential therapeutic target to slow changes that lead to neurodegenerative disorders such as Parkinson”s and Alzheimer”s diseases.

Cell biologists pondering the death of neurons — brain cells — said that by eliminating one ingredient from the cellular machinery, they prolonged the life of neurons stressed by a pesticide chemical.

The researchers, from The University of Texas Health Science Center San Antonio, found that neurons lacking a substance called caspase-2 were better able to withstand pesticide-induced damage to energy centers known as mitochondria.

Alzheimer's disease

Alzheimer's disease

Caspase-2 appears to be a master switch that can trigger either cell death or survival depending on the amount of cellular damage, the team found. Neurons that lacked caspase-2 showed an increase in protective activities, including the efficient breakdown of obsolete or used proteins. This process, called autophagy, delays cell death.

“This research shows, for the first time, that in the absence of caspase-2 neurons increase autophagy to survive,” said study co-author Marisa Lopez-Cruzan, investigator in the cellular and structural biology department at the Health Science Center.

Evidence suggests that mitochondrial dysfunction plays an important role in neuronal death in conditions such as Parkinson”s disease, Alzheimer”s disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig”s disease) and Huntington”s disease.


“Identifying initiators in the cell death process is important for determining therapeutic approaches to provide the maximum protection of neurons during neurodegenerative conditions,” said senior author Brian Herman, Ph.D., vice president for research and professor of cellular and structural biology at the Health Science Center.

The team studied neurons from young adult mice. This was intended to model the early changes that take place in neurodegenerative diseases.

Dr. Lopez-Cruzan, director of Dr. Herman”s laboratory, came up with the idea that caspase-2 protects cells from mitochondrial stress. Meenakshi Tiwari, postdoctoral fellow, expanded upon the initial work and is first author of the paper.

The research is in the March 11 issue of the Journal of Biological Chemistry.