Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD/SIRT1 Pathway

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2025 Jan 8

PMID 39766219

Authors

Riccardo Belardi

Francesca Pacifici

Terenzio Cosio

Sara Lambiase

Ruslana Gaeta Shumak

Fabio Artosi

Antonia Rivieccio

Danilo Cavalloro

Elena Dellambra

Luca Bianchi

David Della-Morte

Elena Campione

Affiliations

Soon will be listed here.

Abstract

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential to prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK progression. NAM is a precursor of nicotinamide adenine dinucleotide (NAD), which activates sirtuin (SIRT)1, a protein with anti-cancer properties. Although the role of SIRT1 in AK is still debated, no data currently exist on the systemic modulation of this protein in AK. Therefore, this study aims to evaluate whether NAM, by increasing serum NAD+ levels, may promote SIRT1 activation in peripheral blood mononuclear cells (PBMCs) in AK patients. Thirty patients were enrolled and treated with NAM for 24 months. Hematological, biochemical, and skin condition assessments were conducted, alongside the measurement of SIRT1 and NAD levels. A decrease in basophils, monocytes, total cholesterol, and blood glucose levels was observed in the study group, along with a reduction in AK lesions. Notably, NAM treatment significantly enhanced serum NAD levels, and nuclear SIRT1 activity in PBMCs. In conclusion, NAM administration significantly reduced AK progression in a NAD/SIRT1-dependent manner, supporting its role as a chemopreventive agent in AK management.

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