Alzheimer's protein markers could transform diagnosis and drug targets
Researchers identified two protein subunits that decline in Alzheimer's disease and could serve as reliable disease indicators, potentially opening new avenues for earlier diagnosis and treatment. The findings suggest these proteins play a protective role against the cellular damage that defines the condition, offering pharmaceutical companies and diagnostic developers a fresh biological target to pursue.
Originaltitel: Stratifying cellular injury in Alzheimer's disease by chaperonin containing TCP1 subunits 2 and 3
Chaperonins complex into double-ringed octamers to aid peptide folding. Recent evidence implicates dysfunctional chaperonin subunits in cancer and neurodegenerative diseases because their deregulation exacerbates cellular injury. Nevertheless, a gap of knowledge exists regarding the expression and localization of chaperonin subunits in relation to amy-loidogenic processes in Alzheimer's disease (AD). Here, we show that reduced levels of chaperonin-containing TCP-1 subunits 2 (CCT2) and 3 (CCT3) stratify AD, with the sub-cellular distribution of their residua being mutually exclusive with both beta-amyloid and hyperphosphorylated tau in neurons. We find CCT3 localized to a subset of glial fibrillary acidic protein-positive astrocytes in AD. Increased oxidative stress in vitro upregulated CCT3 expression in astrocyte-like U251 cells. Conversely, CCT3, but not CCT2, loss-of-function in neuron-like SH-SY5Y cells increased intracellular beta-amyloid load. These data suggest that CCT2/CCT3 are faithful disease-state indicators and implicate CCT3 in oxidative stress-dependent cellular damage pathways.