Forkhead box O-mediated muscle atrophy gene transcripts (FoxO-atrogene mRNAs)

The mRNA transcripts of genes in FoxO-mediated muscle atrophy pathways, often referred to as 'atrogenes,' represent a critical set of targets for treating muscle wasting. The Forkhead box O (FoxO) family of transcription factors, particularly FoxO1, FoxO3, and FoxO4, are the primary regulators of this program (Sandri et al., 2004, Cell). Under conditions of stress, starvation, or disease, these factors translocate to the nucleus and upregulate the expression of E3 ubiquitin ligases such as TRIM63 (MuRF1) and FBXO32 (Atrogin-1/MAFbx), which tag myofibrillar proteins for degradation by the 26S proteasome (Stitt et al., 2004, Molecular Cell). Additionally, FoxO signaling activates the autophagy-lysosome pathway, further accelerating protein breakdown (Milan et al., 2015, Nature Communications). Targeting these mRNA transcripts via RNA interference (RNAi) or antisense oligonucleotides (ASOs) aims to block the production of these degradative enzymes to preserve muscle mass in conditions like cancer cachexia and sarcopenia. However, because FoxO factors also regulate essential processes like glucose metabolism and tumor suppression, therapeutic strategies must carefully balance muscle preservation with potential systemic side effects (Reed et al., 2012, Skeletal Muscle).

Other names

AtrogenesMuscle-atrophy-related gene transcriptsMuRF1 and Atrogin-1 mRNAsTRIM63 and FBXO32 transcripts

Inhibition of translation through RNA interference or antisense oligonucleotides to prevent the synthesis of E3 ubiquitin ligases and other degradative proteins.