| MECHANISM OF ACTION |
Although several researchers believe that the holes--whether they are pores or ion channels--kill cells by interfering with calcium flow, author offers some other possible mechanisms.
In one scenario that he sketches for Parkinson's, protofibrillar alpha-synuclein binds to mitochondrial membranes in neurons, forming pores that permeabilize the membranes, which then leak cytochrome C into the neuronal cytoplasm. It's also possible that permeabilization of vesicular membranes permits dopamine, a cytotoxic neurotransmitter that neurons package in vesicles for safekeeping, to leak into the cytoplasm and kill the neurons. In fact, he says, "there could be 10 things that happen that are bad. The process of a cell dying in these diseases is probably a mess, with lots of different things happening simultaneously. It is important to understand as many of those processes as possible, but they don't represent good independent drug targets. "You don't want to try to individually treat the 10 things that an amyloid pore can do. "Instead, it would be better to block formation of pores in the first place."
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