Thimet oligopeptidase (THOP1) (THOP1)

Thimet oligopeptidase (THOP1), also known as Endopeptidase 24.15, is a 78-kDa zinc-dependent metalloendopeptidase that is ubiquitously expressed in mammalian tissues, with particularly high levels in the brain, testes, and kidneys [4, 9]. It primarily functions within the cytosol but is also found associated with the plasma membrane or secreted into the extracellular space, where it metabolizes various bioactive neuropeptides such as bradykinin, neurotensin, and gonadotropin-releasing hormone (GnRH) [6, 20]. THOP1 is notably involved in the degradation of amyloid-beta (Aβ) peptides, suggesting a neuroprotective role in Alzheimer's disease pathology [1, 17]. Beyond its role in neuropeptide signaling, it participates in MHC class I antigen presentation and has been linked to the regulation of blood pressure and metabolic processes like insulin resistance [4, 6]. Pharmacological targeting of THOP1 with inhibitors like SA-898 aims to modulate these peptide-driven pathways to treat neurodegenerative, cardiovascular, and inflammatory conditions [3, 16].

Other names

Endopeptidase 24.15EP24.15Pz-peptidaseKininase AEndo-oligopeptidase ASoluble metallo-endopeptidaseMP78Thimet peptidase

Competitive inhibition of the zinc-dependent catalytic site to prevent the degradation or activation of specific bioactive peptide substrates.