Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

NAD Metabolism and Proteomic Profile in a Yeast Model Expressing a Neurotoxic polyQ Protein: Effect of Phenolics from Extra-virgin Olive Oil

Silvia Vincenzetti
ORCID logo ,
Yusup Rozimemet
,
Sofia Renzi
,
Daniela Micozzi
,
Dennis Fiorini
ORCID logo ,
Massimo Ricciutelli
ORCID logo ,
Valeria Polzonetti
ORCID logo ,
Stefania Pucciarelli
* ORCID logo
Version 1 : Received: 26 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (19:52:29 CET)

How to cite: Vincenzetti, S.; Rozimemet, Y.; Renzi, S.; Micozzi, D.; Fiorini, D.; Ricciutelli, M.; Polzonetti, V.; Pucciarelli, S. NAD Metabolism and Proteomic Profile in a Yeast Model Expressing a Neurotoxic polyQ Protein: Effect of Phenolics from Extra-virgin Olive Oil. Preprints 2024, 2024021499. https://doi.org/10.20944/preprints202402.1499.v1 Vincenzetti, S.; Rozimemet, Y.; Renzi, S.; Micozzi, D.; Fiorini, D.; Ricciutelli, M.; Polzonetti, V.; Pucciarelli, S. NAD Metabolism and Proteomic Profile in a Yeast Model Expressing a Neurotoxic polyQ Protein: Effect of Phenolics from Extra-virgin Olive Oil. Preprints 2024, 2024021499. https://doi.org/10.20944/preprints202402.1499.v1

Abstract

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Keywords

NAD; NMNAT; NaMN; yeast; ageing; polyQ prototoxicity; Huntingtin; Sirt2; EVOO; polyphenols.

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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