Table 1.
Beneficial and adverse modulations of neuropeptide activities in Alzheimer’s disease.
| Pathway | Target | Ligand or Substrate | Drug with Reference * | Potential Effect |
|---|---|---|---|---|
| HPA | CRFR1 | CRFR1 antagonists | - | + |
| GHRH-GH-IGF1 | GHRH-R | GHRH-R antagnists | - | + |
| HPG | GnRH-R | GnRH-R antagonists or super-agonists | - | + |
| insulin metabolism | IDE | insulin | NA | NA |
| RAAS | ACE | ACE inhibitors | Captopril, etc. [499] | - ? |
| NP metabolism | NEP | NEP inhibitors | Sacubitril [500] | - ? |
| matrix metabolism | MMPs | MMP inhibitors | Periostat [57] | - ? |
| GOAT-ghrelin | ghrelin-R | ghrelin-R agonist | Macimorelin [494] | + |
| BChE | non-selective BChE inhibitors | Rivastigmine, Huperzine-A [495] | + | |
| orexin | OX1R, OX2R | dual OXR antagnists | Suvorexant, Daridorexant, Lemborexant [501] | + |
* FDA-approved drugs capable of passing the blood–brain barrier. ?: potential side effect in the long run; ACE: angiotensin convertase enzyme; BChE: butyrylcholinesterase; CRFR1: corticotrope-releasing factor receptor 1; GHRH: growth hormone-releasing hormone; GHRH-R: growth hormone-releasing hormone receptor; ghrelin-R: ghrelin receptor; GnRH: gonadotropin-releasing hormone; GnRH-R: gonadotropin-releasing hormone receptor; GOAT: ghrelin O-acyltransferase; IDE: insulin-degrading enzyme; NEP: neprilysin; NP: natriuretic peptides; OXR: orexin receptor; OX1R: orexin 1 receptor; OX2R: orexin 2 receptor; RAAS: renin angiotensin aldosterone system.