Last Friday, I discussed drugs that treat the synaptic dysfunction of Alzheimer’s Disease (AD). This week we will look at drugs that aim to safeguard brain neurons by protecting their energy supply. These drugs affect the function of organelles within the cell called mitochondria.
If you remember mitochondria from past Biology classes, the phrase “powerhouse of the cell” may come to mind. The function of mitochondria is to produce ATP molecules, which the cell uses as a form of stored energy.
ATP stands for adenosine-tri-phosphate—basically an adenine nucleotide with three phosphate groups attached. The phosphate groups are highly positively charged. To push three positive phosphate groups together takes a lot of energy, because objects of the same charge repel one another. So energy is used to form the bonds holding ATP together, and can be released by breaking, or cleaving, the bond holding the third phosphate in place.
When neuronal mitochondria become less effective producers of ATP, neurons don’t have the energy they need for metabolism, repair, and signaling. If mitochondrial function is badly impaired, neurons die.
Looking for drugs that protect organelle function is a new approach to treating Alzheimer’s Disease, but it makes sense. Mitochondria dysfunction occurs early in AD and promotes synaptic damage as well as neurodegeneration. Furthermore, amyloid proteins can interact with the mitochondria to cause even more impairment in the brain.
When researchers began to study mitochondria in AD, they found that some drugs already in use (Donepezil and Memantine) helped preserve mitochondial structure and enhanced mitochondrial function. How much of their effectiveness in AD is due to mitochondrial protection and how much to receptor blockade is not yet clear.
One new drug that enhances mitochondrial function is currently being tested on AD patients. Thus far it appears that this drug, Latrepirdine, is effective and improves overall well-being in people with AD.