This paper is interesting. It’s not substantial.
I take it as a grain of salt. No, I don’t like it at all.
They were seeing reduced level of an metabolic enzyme Cystathionine γ-lyase (CSE), which makes cysteine and hydrogen sulfide in three models of huntington’ disease: cell lines, mouse models and post-mortem patient samples. And CSE KO mice exhibits certain behavior deficits resembling HD symptoms. Replenishing cysteine in diet alleviates these behavior deficits and increases survival.
First of all, it’s an interesting observation of a reduced level of CSE in HD models——perhaps among hundreds of other random proteins. There is no evidence suggesting CSE activity loss or global reduction in cysteine level, in any way, contributes to disease onset/progression.
Actually they can’t tell if cysteine is the culprit here. CSE makes both cysteine and hydrogen sulfide, and we know that H2S is an important second messenger in signaling in the brain and periphery. That cysteine rescue experiment does not rule out H2S function in the disease state.
The biggest problem I have with this study is all the behavior assay. They were trying to use a few of the standard motor tests to model HD, which is just not nearly satisfying at all. Who knows what causes these deficits when you deplete one of the nine essential amino acids ? It totally doesn’t have to be, in any way, Huntington-dependent, and these tests are not at all good means to monitor HD pathophysiology.
What should they do? Well, since it’s just too vague a connection between CSE expression and some random motor behavior tests, anything in between is essential and the more, the better. At least they should’ve looked at some cellular phenotypes including cell death, inclusion body aggregates and neurodegeneration. Some metabolic profiling and behavior are also welcomed.