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Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes [Medical Sciences]

Radiation therapy for head and neck cancer often leads to dry mouth, a debilitating condition that affects speaking, swallowing, and other functions related to quality of life. Since salivary functional recovery after radiation is largely dependent on the number of surviving salivary stem/progenitor cells (SSPCs), we reasoned that protection of SSPCs from injury is critical for mitigating dry mouth. Following radiation, SSPCs accumulate toxic aldehydes that damage DNA, proteins, and lipids, leading to cell death. Here, we identified d-limonene as an activator of aldehyde dehydrogenase 3A1 (ALDH3A1) with a favorable safety profile for clinical use. ALDH3A1 activation decreases aldehyde accumulation in SSPCs, increases sphere-forming ability, reduces apoptosis, and preserves salivary gland structure and function following radiation without reducing the anticancer effects.

Authors:   Julie P. Saiki; Hongbin Cao; Lauren D. Van Wassenhove; Vignesh Viswanathan; Joshua Bloomstein; Dhanya K. Nambiar; Aaron J. Mattingly; Dadi Jiang; Che-Hong Chen; Matthew C. Stevens; Amanda L. Simmons; Hyun Shin Park; Rie von Eyben; Eric T. Kool; Davud Sirjani; Sarah M. Knox; Quynh Thu Le; Daria Mochly-Rosen
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   24
Year:   2018
Pages:   6279
DOI:   10.1073/pnas.1802184115
Publication date:   12-Jun-2018
Facts, background information, dossiers
  • aldehydes
More about Proceedings of the National Academy of Sciences
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