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Figueroa RA, Ramberg V, Gatsinzi T, et al. Anchored FRET sensors detect local caspase activation prior to neuronal degeneration. Mol Neurodegener. 2011;6(1):35doi: 10.1186/1750-1326-6-35.
Figueroa, R. A., Ramberg, V., Gatsinzi, T., Samuelsson, M., Zhang, M., Iverfeldt, K., & Hallberg, E. (2011). Anchored FRET sensors detect local caspase activation prior to neuronal degeneration. Molecular neurodegeneration, 6(1), 35. https://doi.org/10.1186/1750-1326-6-35
Figueroa, Ricardo A, et al. "Anchored FRET sensors detect local caspase activation prior to neuronal degeneration." Molecular neurodegeneration vol. 6,1 (2011): 35. doi: https://doi.org/10.1186/1750-1326-6-35
Figueroa RA, Ramberg V, Gatsinzi T, Samuelsson M, Zhang M, Iverfeldt K, Hallberg E. Anchored FRET sensors detect local caspase activation prior to neuronal degeneration. Mol Neurodegener. 2011 May 23;6(1):35. doi: 10.1186/1750-1326-6-35. PMID: 21605370; PMCID: PMC3121597.
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Mol Neurodegener. 2011 May 23;6(1):35. doi: 10.1186/1750-1326-6-35.

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

Molecular neurodegeneration

Ricardo A Figueroa, Veronica Ramberg, Tom Gatsinzi, Malin Samuelsson, Mu Zhang, Kerstin Iverfeldt, Einar Hallberg

Affiliations

  1. Department of Neurochemistry, Stockholm University, SE-106 91 Stockholm, Sweden. [email protected].

PMID: 21605370 PMCID: PMC3121597 DOI: 10.1186/1750-1326-6-35

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 different stimuli. Interestingly, after staurosporine treatment caspase-6 activation was significantly delayed in neurites compared to cell bodies. In addition, we show that exposure to oligomer-enriched amyloid-β peptide resulted in loss of FRET in cells expressing sensors for caspase-3 and -6, but not -9, in both soma and neurites before neurite degeneration was observed.

CONCLUSIONS: Taken together, the results show that by using anchored FRET sensors it is possible to detect stimuli-dependent differential activation of caspases and to distinguish local from global caspase activation in live neuronal cells. Furthermore, in these cells oligomer-enriched amyloid-β peptide induces a global, rather than local activation of caspase-3 and -6, which subsequently leads to neuronal cell death.

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