Aspirin, or acetylsalicylic acid, has been the most widely used
medication across the globe for the past two centuries to prevent platelet
aggregation and to treat symptoms of pain, fever, and inflammation. With so
many pharmacological effects, researchers at Boyce Thompson Institute and John
Hopkins University sought to identify all of aspirin’s actions. The primary
metabolite of aspirin, salicylic acid (SA), was found to target several
human proteins in a high-throughput screen of SA binding activity; glyceraldehyde
3-phosphate dehydrogenase (GAPDH) was one of the proteins discovered to be a
target of SA.
GAPDH is well-known for facilitating the production of
energy from glucose. In addition to catalyzing the sixth step of glycolysis,
GAPDH has been implicated to aid in transcription activation, DNA repair, and
more recently, to initiate apoptosis and cell death. GAPDH’s apoptotic actions
affect multiple cell types, most interestingly neuronal cells in the presence of
reactive oxygen species (ROS). GAPDH therefore is a major suspect in neurodegenerative
diseases including Huntington’s, Parkinson’s, and Alzheimer’s diseases.
Under oxidative stress, such as in excess of the ROS nitric
oxide and other reactive compounds, GAPDH enters the nucleus of a neuron where
it then upregulates the transcription of inappropriate proteins. This distorted
production of proteins initiates the apoptosis cascade, kills the cell, and eventually
results in the neurodegeneration of the individual. SA, similarly to a current anti-Parkinson’s
drug (deprenyl), prevents the modification of GAPDH that allows it to enter a
neuron’s nucleus, thus preventing the downstream death of that neuron.
The suggested neuroprotective properties of SA led researchers
to investigate additional compounds that have a greater affinity for GAPDH than
aspirin-derived SA and found that SA in licorice, a Chinese medicinal herb, better
binds GAPDH. Researchers are currently screening for even more potent forms of
SA, anticipating that a stronger compound will exhibit greater ability to
suppress GAPDH’s entry into neural nuclei and potentially arrest
neurodegenerative diseases.
Here is a link to the study!
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143447
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