20.500.12556/DiRROS-31033 Celični modeli nevrodegeneracije in nevrovnetja kot orodje predkliničnih raziskav primer zaviralca katepsina X Cellular models of neurodegeneration and neuroinflammation as tools for preclinical research the case of a cathepsinX inhibitor Nevrodegenerativne bolezni, kot sta Alzheimerjeva bolezen in Parkinsonova bolezen, so povezane s progresivno izgubo nevronov, pri čemer nevrovnetje deluje kot ključni pospeševalec degenerativnih procesov. V raziskavi smo vzpostavili in ovrednotili sklop celičnih modelov za ponovljivo posnemanje ključnih procesov nevrodegeneracije in nevrovnetja ter funkcionalno vrednotenje spojin vodnic. Vključili smo model Alzheimerjeve bolezni, model Parkinsonove bolezni in modele nevrovnetja v celicah glije, tj. mikrogliji, astrocitih in oligodendrocitih, ki pomembno sodelujejo pri vnetnih procesih v osrednjem živčevju. Na vzpostavljenih modelih smo ovrednotili spojino AMS36, zaviralec katepsina X, z obetavnim zaščitnim učinkom na poškodovane nevrone in protivnetnim delovanjem. V celičnih modelih smo spremljali spremembe celičnega fenotipa, izražanje specifičnih celičnih označevalcev, stopnjo celične poškodbe ter aktivacijo poti apoptoze. Rezultati so potrdili ustreznost vzpostavljenih modelov, kar se odraža v povzročeni poškodbi celic in vnetnem odzivu, ter pokazali, da AMS36 poveča preživetje celic, zmanjša kazalce apoptoze in ublaži vnetni odziv. Predstavljeni sklop modelov predstavlja uporabno predklinično platformo za usmerjeno vrednotenje kandidatnih učinkovin pri procesih nevro degeneracije in nevrovnetja. Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are associated with progressive neuronal loss, with neuroinflammation acting as a key driver that accelerates degeneration. In this study, we established and validated a set of cellular models to reproducibly mimic key aspects of neurodegeneration and neuroinflammation and to enable functional evaluation of lead compounds. The set included an Alzheimer’s disease model, a Parkinson’s disease model, and neuroinflammation models in glial cells, namely microglia, astrocytes, and oligodendrocytes, which play important roles in inflammatory processes in the central nervous system. Using these models, we evaluated AMS36, a cathepsin X inhibitor, with promising neuroprotective effects on injured neurons and anti-inflammatory activity. Across the established models, we monitored changes in cellular phenotype, expression of specific cellular markers, the extent of cellular injury, and activation of apoptotic pathways. The results confirmed the suitability of the models, reflected by induced cellular damage and an inflammatory response, and showed that AMS36 increases cell survival, reduces apoptotic markers, and attenuates the inflammatory response. The presented set of models provides a useful preclinical platform for targeted evaluation of candidate compounds in the context of neurodegeneration and neuroinflammation. celični modeli nevrodegeneracija nevrovnetje zaviralec katepsina X cathepsin X inhibitor cellular models neurodegeneration neuroinflammation true false true Slovenski jezik Angleški jezik Neznano 2026-07-10 11:52:18 2026-07-10 11:52:18 2026-07-11 03:51:13 0000-00-00 00:00:00 2026 0 0 Opis vira z dne 19. 5. 2026; Nasl. z nasl. zaslona; str. 91-101 št. 2 Letn. 77 maj 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2026-05-01 616.831-003.8+616-002 2536-4316 278573315 selena.pdf selena.pdf 1 A82A1A2BE6D665B063D2AFB5462E4068 efd25bad1d9090f6fa7231c033e3f8200d37a149c5ad5d0d85b33c4a61205154 0a5573bc-7c45-11f1-b663-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=47808 Slovensko farmacevtsko društvo 0 0 0