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Effects of curcumin nanoformulations on cellular function in Niemann-Pick disease type C astrocytes

Emily Maguire, Luke J. Haslett, Joanne L. Welton, Helen Waller-Evans, Jule Goike, Emily H. Clark, Harry R. Knifton, Ravin Shrestha, Kim Wager, Richard Webb, Emyr Lloyd-Evans
doi: https://doi.org/10.1101/135830
Emily Maguire
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Luke J. Haslett
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Joanne L. Welton
2Department of Biomedical Sciences, Cardiff Metropolitan University, Llandaff Campus, Western Avenue, Cardiff, CF5 2YB, United Kingdom
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Helen Waller-Evans
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Jule Goike
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Emily H. Clark
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Harry R. Knifton
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Ravin Shrestha
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Kim Wager
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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Richard Webb
2Department of Biomedical Sciences, Cardiff Metropolitan University, Llandaff Campus, Western Avenue, Cardiff, CF5 2YB, United Kingdom
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Emyr Lloyd-Evans
1School of Biosciences, Sir Martin Evans Building, Cardiff University, Museum Avenue, Cardiff, CF10 3AX. United Kingdom
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  • For correspondence: Lloyd-EvansE@cardiff.ac.uk
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Abstract

Niemann-Pick disease type C1 (NPC disease) is a neurodegenerative multi-lipid lysosomal storage disease caused by mutations in the NPC1 gene presenting with reduced lysosomal Ca2+ signalling and inhibited late endosome-lysosome transport. Elevating cytosolic Ca2+ levels in NPC cells has been shown to reduce lysosomal lipid storage. Treating Npc1-/- mice with the Ca2+ modulator curcumin led to reduced lipid storage, improved life expectancy and function. These studies led to reported utilisation of curcumin supplements by NPC disease families despite there being no clinical evidence of benefit and a report indicating no benefit of nanoformulated curcumin in Npc1-/- mice. The aim of this study was to determine whether various commercially available curcumin nanoformulations were capable of reproducing the findings obtained with unformulated pharmaceutical grade curcumin. We compared seven curcumin nanoformulations in Npc1-/- mouse astrocytes. All the nanoformulations elevate cytosolic Ca2+ levels but only two lowered lysosomal lipid storage. Importantly, some caused elevations in NPC lysosomal storage and/or decreased cellular viability. Although this is an in vitro study, our findings suggest that care should be taken when contemplating the use of curcumin supplements for NPC disease.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 09, 2017.
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Effects of curcumin nanoformulations on cellular function in Niemann-Pick disease type C astrocytes
Emily Maguire, Luke J. Haslett, Joanne L. Welton, Helen Waller-Evans, Jule Goike, Emily H. Clark, Harry R. Knifton, Ravin Shrestha, Kim Wager, Richard Webb, Emyr Lloyd-Evans
bioRxiv 135830; doi: https://doi.org/10.1101/135830
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Effects of curcumin nanoformulations on cellular function in Niemann-Pick disease type C astrocytes
Emily Maguire, Luke J. Haslett, Joanne L. Welton, Helen Waller-Evans, Jule Goike, Emily H. Clark, Harry R. Knifton, Ravin Shrestha, Kim Wager, Richard Webb, Emyr Lloyd-Evans
bioRxiv 135830; doi: https://doi.org/10.1101/135830

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