Akademik Veri Yönetim Sistemi
Federation of European Neuroscience Societies, cilt.1, sa.1, ss.1-2, 2024 (Düzenli olarak gerçekleştirilen hakemli kongrenin bildiri kitabı)
Hyperlipidemia is a risk factor for developing atherosclerosis and
neurodegenerative disorders, however, the underlying molecular mechanisms
are not well understood. Protein Kinase R-like Endoplasmic Reticulum
Kinase (PERK) signaling is one of the molecular pathways thought to be
involved in hyperlipidemia-driven neurodegeneration. Studies indicate
that mitophagy, regulated by phosphatase tension homolog-induced
kinase-1 (PINK1) and Parkin, is crucial for removing damaged
mitochondria; otherwise, this can lead to disrupted mitochondrial
function. Increased cholesterol levels impair mitophagy in conjunction
with cardiovascular disease. According to one study, lipid-induced PERK
increases in Lon protease-1 (LONP1), degrades PINK1, and suppresses
mitophagy in macrophages, and PERK inhibition reverses these effects.
Currently, we investigated whether the brains of hyperlipidemic mice
exhibit these outcomes. We evaluated the impacts of differing
cholesterol levels in the hippocampus of C57BL/6 and Apoe-/- mice that
were given either a western or chow diet. Inhibitors of the PERK
pathway, GSK2606414, and ISRIB, were administered to western diet-fed
Apoe-/- mice. Protein expression levels of LONP1, PINK1, and Parkin were
examined in hippocampal mitochondrial lysates by Western blotting.
Preliminary evidence showed that increased cholesterol levels, as well
as inhibition of the PERK pathway, didn’t alter these markers in the
hippocampus. Remarkably, this pattern differed from that observed in
macrophages, implying that hyperlipidemia-induced PERK signaling might
not suppress mitophagy in the hippocampus. Further analysis is being
conducted to validate these findings and provide a better understanding
of these inhibitors as therapeutics.