Brain chemical blamed for cell death

USA Today (Society for the Advancement of Education), Oct, 1996

By chemically synthesizing and studying the brain chemical dopegal in a tissue culture model of brain neurons, researchers at Saint Louis University School of Medicine have shown how the substance becomes toxic and accumulates in the cell, delivering a suicide message to brain cells in degenerative conditions such as Alzheimer's dementia. Neurons are the cells that carry out the functions of the brain, consisting of a cell body that contains genetic instructions together with the cell's biosynthetic machinery and a long projection called an axon, which reaches to the next neuron in the circuit. Neurons communicate with each other by chemicals called neurotransmitters that are transported from the cell body to the axon terminals where they are released. Neurotransmitters are the chemical messengers ultimately responsible for controlling memory, mood, movement, and behavior. When a neurotransmitter sends a message, a chemical stop order also must be conveyed to break the neurotransmission.

With a particular neurotransmitter, norepinephrine, dopegal is the first step in a sequence of chemical changes that stops message transmission. Under normal circumstances, dopegal is formed in the axon terminals away from the cell's genetic instructions that contain a program for cell suicide, so it can not trigger the suicide message. In Alzheimer's disease, however, there is a block in the transport system which carries the neurotransmitters to the axon terminals. Consequently, a toxic level of dopegal accumulates in the cell body, where it triggers cell death.

This faulty transport process is what may be responsible for cell death in degenerative diseases such as Alzheimer's. By knowing where the sequence goes awry, researchers can find ways to stabilize the transport system, keeping it in good repair. This will allow dopegal to be moved away from the cell's genetic instructions and to be altered further to nontoxic chemicals.