Neuropeptide Y messenger RNA (NPY mRNA)

Neuropeptide Y (NPY) messenger RNA (mRNA) is the genetic template for the synthesis of Neuropeptide Y, one of the most abundant and potent orexigenic (appetite-stimulating) peptides in the mammalian brain (Tatemoto et al., 1982). Primarily synthesized in the arcuate nucleus of the hypothalamus, NPY mRNA levels are highly responsive to energy status, increasing during fasting to promote food seeking and energy conservation (Stephens et al., 1995). Beyond its role in metabolism, NPY is a key regulator of the stress response, circadian rhythms, and cardiovascular function (Heilig, 2004). As a therapeutic target, NPY mRNA is approached using nucleic acid-based technologies such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to downregulate NPY production in specific brain regions (Akabayashi et al., 1994). This approach is being explored for the treatment of obesity and metabolic disorders where NPY is overexpressed. However, the widespread physiological roles of NPY and the difficulty of delivering large, charged molecules across the blood-brain barrier present significant hurdles for clinical development (Wahlestedt et al., 1993).

Other names

Neuropeptide Y transcriptNPY mRNAPreproneuropeptide Y mRNA

Antisense oligonucleotides or siRNA molecules bind to the NPY mRNA sequence, leading to its degradation via RNase H or the RISC complex, thereby preventing the translation of the NPY peptide (Wahlestedt et al., 1993; Akabayashi et al., 1994).