Putative identification of CASTOR1 as one of the targets of ganoderic acid a via thermal proteome profiling and...

In traditional Chinese medicine theory, aging is hypothesized to arise from severe deficiency of kidney essence, which is posited to induce "emptiness of the sea of marrow". Ganoderma has been documented to possess properties that nourish kidney qi and enrich essence and blood. It has been demonstrated that ganoderma triterpenoids are capable of mitigating age-related cerebral atrophy and retarding the aging process in murine models. Ganoderic acid A (GAA) has been characterized as the principal bioactive metabolite of these triterpenoids. Leveraging thermal proteomics profiling, CASTOR1 was identified as a target protein exhibiting significant disparities in melting curves. Through functional annotation via GO terms and pathway analysis using KEGG, it has been indicated that GAA may modulate metabolic regulatory pathways through interaction with specific molecular targets. A pronounced association between GAA and the GATOR2 complex, a downstream effector of CASTOR1, has been revealed by GO enrichment analysis, suggesting a potential mechanistic link. Thus, it is inferred that one potential target of GAA in neuronal cells is presumably CASTOR1 protein. It is hypothesized that ganoderic acid A exerts its pharmacological effects likely through regulation mediated by the potential target protein CASTOR1, which in turn modulates the mTOR signaling pathway.