An FDA approved drug reduces energy requirements in neurons. Relieved from the pressure of protein production the neuron can use energy for cellular repair.
In 2016 researchers at the Salk Institute for Biological Studies published a paper on the use of rapamycin on brain cells grown in a Petri dish. These brain cells were derived from patients with a mitochondrial disorder that results in reduced energy production. Energy depleted cells are unable to keep up with self repair and eventually self destruct. However, with protein production reduced, the neurons were able to shift energy (ATP) for self repair processes.
The researchers surmise that “a rapamycin-induced decrease in protein synthesis, a major energy-consuming process, may account for its ATP-saving effect.” They “propose that a mild reduction in protein synthesis may have the potential to treat mitochondria-related neurodegeneration.”
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Patients with maternally inherited Leigh syndrome, or MILS, donated skin samples that were coaxed into brain cells. These neurons were treated with rapamycin which increases their resistance to glutamate toxicity.
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system and is involved in learning in memory. As with all proteins and molecules in cells there is production and recycling. Without adequate recycling of glutamate the neurotransmitter builds up to toxic levels, which in turn causes a number of enzymes to over activate and damage the neurons.
In our cells a protein called mTOR (mechanistic target of rapamycin) monitors the levels of oxygen, nutrients, and energy (ATP). Rapamycin inhibits mTOR so that it doesn’t detect the full amount of the above ingredients and so ramps down protein production.
The ATP not being used up by protein production can then be used for the phosphorylation of glutamate. Because protein homeostasis is often distorted in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, this use of rapamycin to restore protein homeostasis could provide some protection.
While some studies have looked at protecting neurons by increasing ATP production in mitochondria, this study shows that reducing energy use to match ATP production can prolong the life of the neuron.