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bioRxiv · 10.64898/2026.05.10.724132

Stratifying cellular injury in Alzheimer's disease by chaperonin containing TCP1 subunits 2 and 3

Mulder, J.·Hortobagyi, T.·Harkany, T.
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Abstract

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 amyloidogenic processes in Alzheimers disease (AD). Here, we show that reduced levels of chaperonin-containing TCP-1 subunits 2 (CCT2) and 3 (CCT3) stratify AD, with the subcellular 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.

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Mulder, J., Hortobagyi, T., Harkany, T.. 2026-05-13. Stratifying cellular injury in Alzheimer's disease by chaperonin containing TCP1 subunits 2 and 3. https://doi.org/10.64898/2026.05.10.724132

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