Anchored FRET sensors detect local caspase activation prior to neuronal degeneration.

ABSTRACT:

Background

Recent studies indicate local caspase activation in dendrites or axons during development and in neurodegenerative disorders such as Alzheimer's disease (AD). Emerging evidences point to soluble oligomeric amyloid-β peptide as a causative agent in AD.

Results

Here we describe the design of fluorescence resonance energy transfer (FRET)-based caspase sensors, fused to the microtubule associated protein tau. Specific caspase sensors preferentially cleaved by caspase-3, -6 or -9 were expressed in differentiated human neuroblastoma SH-SY5Y cells. The anchoring of the sensors resulted in high FRET signals both in extended neurites and soma and made analysis of spatiotemporal signal propagation possible. Caspase activation was detected as loss of FRET after exposure to d

SUBMITTER: Figueroa RA 

PROVIDER: S-EPMC3121597 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature