The proteins that the proteostasis hallmark talks about refers to proteins like beta-amyloid and tau that misfold and subsequently form aggregates. Proteins that are crosslinked aren’t misfolded but rather they become “glued” together by a chemical reaction and don’t form aggregates. 7-KC isn’t a protein and doesn’t misfold; it’s an oxidized lipid.
Edited my comment slightly before yours appeared. Wanted to specify the reasons more but resolved to delete them since I was going to modify the post anyway. The rationale was that 7-KC, even if not a protein, is still an aggregate that overwhelms lysosomes and actively causes their dysfunction (loss of function of lysosomes and other degradation mechanisms being accounted for in the loss of proteostasis paragraphs in the Hallmarks).
If you still feel unsure about the 7-KC thing, the following reasons should put your doubts to rest:
1) Although 7-KC accumulates, it doesn’t aggregate.
2) If Hallmarks really thought that lipid accumulation belonged to the proteostasis hallmark it would have said so.
3) Hallmarks completely ignores 7-KC as a causative factor of atherosclerosis and instead ties atherosclerosis to “uncontrolled cellular overgrowth or hyperactivity” which is nonSENSical.
The proteins that the proteostasis hallmark talks about refers to proteins like beta-amyloid and tau that misfold and subsequently form aggregates. Proteins that are crosslinked aren’t misfolded but rather they become “glued” together by a chemical reaction and don’t form aggregates. 7-KC isn’t a protein and doesn’t misfold; it’s an oxidized lipid.
Edited my comment slightly before yours appeared. Wanted to specify the reasons more but resolved to delete them since I was going to modify the post anyway. The rationale was that 7-KC, even if not a protein, is still an aggregate that overwhelms lysosomes and actively causes their dysfunction (loss of function of lysosomes and other degradation mechanisms being accounted for in the loss of proteostasis paragraphs in the Hallmarks).
If you still feel unsure about the 7-KC thing, the following reasons should put your doubts to rest:
1) Although 7-KC accumulates, it doesn’t aggregate.
2) If Hallmarks really thought that lipid accumulation belonged to the proteostasis hallmark it would have said so.
3) Hallmarks completely ignores 7-KC as a causative factor of atherosclerosis and instead ties atherosclerosis to “uncontrolled cellular overgrowth or hyperactivity” which is nonSENSical.