Men have a higher incidence of specific types of cancer and neurodegenerative disease. Mounting evidence suggests that androgen receptor (AR)-mediated androgen signaling is a key determinant at the core of this sex discrepancy. Herein we review the role of androgens in disorders characterized by altered AR activity, focusing on transcriptional coregulators that shape receptor specificity. In particular, we highlight the roles of protein arginine methyltransferase 6 (PRMT6) and lysine-specific demethylase 1 (LSD1), enzymes associated with epigenetic repression, yet functioning as AR coactivators. By enhancing AR transcriptional output, PRMT6 and LSD1 contribute to malignant transformation and progression across multiple cell types. We further explore how these insights inform combinatorial therapeutic strategies targeting AR, PRMT6, and LSD1, with implications for both cancer and neurodegeneration.

Men have a higher incidence of specific types of cancer and neurodegenerative disease. Mounting evidence suggests that androgen receptor (AR)-mediated androgen signaling is a key determinant at the core of this sex discrepancy. Herein we review the role of androgens in disorders characterized by altered AR activity, focusing on transcriptional coregulators that shape receptor specificity. In particular, we highlight the roles of protein arginine methyltransferase 6 (PRMT6) and lysine-specific demethylase 1 (LSD1), enzymes associated with epigenetic repression, yet functioning as AR coactivators. By enhancing AR transcriptional output, PRMT6 and LSD1 contribute to malignant transformation and progression across multiple cell types. We further explore how these insights inform combinatorial therapeutic strategies targeting AR, PRMT6, and LSD1, with implications for both cancer and neurodegeneration.