Comment by kidel001
8 hours ago
I am surprised they end on a gene mutation already known to be involved in a rare disease and a vague hypothesis about the mechanism. Among the many things DCTN1 does... it also directs autophagosomes toward lysosomes for waste degradation. Hm, disruptions in waste degradation.. build up of unwanted proteins and waste in cells... yeah that seems like it would cause neurodegeneration as well! Point being, there are dozens of things, maybe hundreds. Is cholesterol particularly compelling here? Not really. PhD students come up with similar hypotheses every hour. Hypotheses are cheap. I'm sure it can and will do better, but for now... I feel they might be underprepared for curing all disease in 10 years.
and we do know that cholesterol build-up is linked with reduced mobility:
'Late endocytic vesicles loaded with cholesterol lose their dynamic properties, and become essentially immobile'
https://link.springer.com/article/10.1093/emboj/21.6.1289
we also know that blocking cholesterol in viruses leads the cholesterol-stuffed lysosomes to recruit DCTN1
https://www.nature.com/articles/s41467-024-50711-4
but I can't find anything that links a DCTN1 downregulation directly - as you say, this is a hypothesis a PhD student comes up with during literature review.
The last section of the press release was definitely written by AI. I'm talking about the section that starts with "Finding the next experiment worth doing" all the way to the end.