Tag Archives: neurodegenerative diseases

As we age or develop neurodegenerative diseases such as Alzheimer’s, our brain cells may not produce sufficient energy to remain fully functional. Researchers have discovered that an enzyme called SIRT3 that is located in mitochondria — the cell’s powerhouse — may protect mice brains against the kinds of stresses believed to contribute to energy loss. Furthermore, mice that ran on a wheel increased their levels of this protective enzyme.

Researchers used a new animal model to investigate whether they could aid neurons in resisting the energy-depleting stress caused by neurotoxins and other factors. They found the following:

  • Mice models that did not produce SIRT3 became highly sensitive to stress when exposed to neurotoxins that cause neurodegeneration and epileptic seizures.
  • Running wheel exercise increased the amount of SIRT3 in neurons of normal mice and protected them against degeneration; in those lacking the enzyme, running failed to protect the neurons.
  • Neurons could be protected against stress through use of a gene therapy technology to increase levels of SIRT3 in neurons.

These findings suggest that bolstering mitochondrial function and stress resistance by increasing SIRT3 levels may offer a promising therapeutic target for protecting against age-related cognitive decline and brain diseases.  The research team report their findings online Nov. 19 in the journal Cell Metabolism.

Source: Johns Hopkins Medicine

A new study finds that a component of aspirin binds to an enzyme called GAPDH, which is believed to play a major role in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases.

Researchers discovered that salicylic acid, the primary breakdown product of aspirin, binds to GAPDH, thereby stopping it from moving into a cell’s nucleus, where it can trigger the cell’s death. The study, which appears in the journal PLOS ONE, also suggests that derivatives of salicylic acid may hold promise for treating multiple neurodegenerative diseases.

The researchers performed high-throughput screens to identify proteins in the human body that bind to salicylic acid. GAPDH, (Glyceraldehyde 3-Phosphate Dehydrogenase), is a central enzyme in glucose metabolism, but plays additional roles in the cell. Under oxidative stress—an excess of free radicals and other reactive compounds—GAPDH is modified and then enters the nucleus of neurons, where it enhances protein turnover, leading to cell death.

The anti-Parkinson’s drug deprenyl blocks GAPDH’s entry into the nucleus and the resulting cell death. The researchers discovered that salicylic acid also is effective at stopping GAPDH from moving into the nucleus and preventing cell death.

“The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signaling,” said co-author Solomon Snyder, professor of neuroscience at Johns Hopkins University in Baltimore. “The new study establishes that GAPDH is a target for salicylate drugs related to aspirin, and hence may be relevant to the therapeutic actions of such drugs.”

Source: Boyce Thompson Institute