Alda-1 can reactivate a mutated form of the enzyme ALDH2
ALDH2: ALDH2 is an enzyme that plays an important role in metabolizing alcohol and other toxins, including those created by a lack of oxygen in the wake of a heart attack. It also is involved in the metabolism of nitroglycerin, which is used to prevent chest pain (angina) caused by restricted blood flow and oxygen to the heart. People who carry a mutated form of the enzyme ALDH2 that does not carry out its intended functions well are at increased risk of cardiovascular damage.
Work done by scientists at Stanford and Indiana universities
Back in 2008, a research team at Stanford and Indiana universities schools of medicine, led by Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford, performed a study to understand cardioprotection to heart muscle cells from heart attack damage. The researchers found that a cellular signaling system activated ALDH2 that helps reduce heart muscle damage. They also found that a compound called Alda-1 could bypass the signaling process and activate the enzyme ALDH2 directly.
Now a team, led by Thomas Hurley, Ph.D., associate chair and professor of biochemistry and molecular biology at Indiana University, and Daria Mochly-Rosen, at Stanford, have discovered that the compound, Alda-1 can reactivate a mutated form of the enzyme ALDH2 to help ALDH2 enzyme carry out its intended functions well. They found that Alda-1 acts much like a shim to prop up a mutated form of ALDH2, restoring the enzyme’s function. Dr. Hurley says, “Because of the mutation in the gene, parts of the protein structure become loose and floppy. Alda-1 reactivates the enzyme by propping up those parts of the structure so they regain normal function.”
According to the researchers Alda-1 could lead to a new class of drugs to help reduce the muscle damage caused by heart attacks. According to Dr. Hurley, determining how the Alda-1 compound works will enable the researchers to begin working on alternative compounds that hold more promise as potential drugs. One primary improvement needed is the ability to give the drug orally, rather than by injection. He said, “Based on the information from these studies, we’re now ready to sit down with medicinal chemists and start designing new analogues by applying our understanding of what we need to leave alone and what we can modify to improve the properties of Alda-1.” Dr. Hurley predicted that alternative compounds could be available for testing by mid-2010.
Source: http://communications.medicine.iu.edu/body.cfm?id=106&oTopID=38
January 11, 2010