Key result
Clusterin binds TTR oligomers and is decreased in FAP patients, suggesting protection against aggregate formation.
Why the study?
The role of the extracellular chaperone clusterin in familial amyloidotic polyneuropathy (FAP) and its involvement in transthyretin aggregate formation was unclear.
Clusterin may play a protective role in familial amyloidotic polyneuropathy by modulating transthyretin aggregate formation.
Hypothesis-generating for clusterin-targeted therapies in FAP; leaves open clinical translation pending human studies.
Extracellular chaperones, such as clusterin, have been proposed to contribute to extracellular protein homeostasis. In Alzheimer's disease (AD), clusterin was suggested to be involved in fibrillogenesis and extracellular misfolded protein clearance. Here, we study the relevance of clusterin in familial amyloidotic polyneuropathy (FAP). Analysis of clusterin levels by ELISA showed decreased levels in asymptomatic and in FAP patients, which could be regarded as a consequence of clusterin mobilization to tissues. Incubation of a neuroblastoma cell line with transthyretin (TTR) oligomers resulted in secretion of clusterin into the media and binding to oligomeric species, not observed in parallel experiments with soluble TTR. Overall, our results allow us to postulate a putative protective role of clusterin in FAP, namely in the modulation of TTR aggregate formation. Future experiments are required to clarify the role of clusterin in FAP.
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Magalhães et al. (2012) studied Familial amyloidotic polyneuropathy (FAP). Clusterin was evaluated on Clusterin levels and binding to transthyretin (TTR) oligomers. Clusterin levels were decreased in asymptomatic and FAP patients, and in vitro studies showed clusterin binds to transthyretin oligomers, suggesting a protective role in aggregate formation.
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