An interesting hypothesis on the selection of glucose as major fuel source in neurons

Earlier this year, I wondered why neurons preferentially use glucose as fuel. I have now found an interesting paper by Dave Speijer regarding this problem. He proposes the following reasoning to explain this observation:

reactive oxygen species are generated in large amounts by NADH dehydrogenase (complex I) when the amount of oxidized ubiquinone is limited

generation of large amounts of FADH₂ increases the rate of reduction of ubiquinone, and therefore increases indirectly the amount of harmful radical species generated by NADH dehydrogenase

glucose oxidation generates a much smaller amount of FADH₂ than fatty-acid oxidation. Therefore:

Especially vulnerable cells may be expected to have evolved a preference for glucose.

Incidentally, neurons do seem to lack large amounts of one of the enzymes involved in fatty acid oxidation: thiolase.