Targeting Acetylcholinesterase with Oxytocin: A New Avenue in Alzheimer’s Disease Therapeutics

Oxytocin, the so-called natural love hormone, is a neuropeptide comprising nine amino acids with an active aliphatic disulfide bond forming the cyclic ring through cysteine¹-cysteine⁶ residues. Oxytocin synthesizes in hypothalamus and acts as a neurotransmitter. Oxytocin receptors are present in many areas of brain such as the hypothalamus that involve in the pathophysiology of Alzheimer’s disease (AD). Since 1987, it has been postulated that oxytocin could be useful in the treatment of AD as it showed some positive outcomes when injected into the hypothalamus in experimental animals. However, in recent years, some reports suggested that oxytocin decreases the amyloid-β (Aβ) and tau deposition in AD animal experiments and exhibited antioxidant and anti-inflammatory properties, therefore, acting as a neuroprotective agent. In addition, even though evidence is limited, recently, it has also been reported that oxytocin is capable of inhibiting acetylcholinesterase (AChE) and can reverse learning and memory impairment in AD animal models but the in vitro enzyme inhibition data have not been reported yet. Therefore, as it is well documented that AChE inhibition leads to an increase of acetylcholine level and a decrease of Aβ and tau deposition in brain, discovery and development of oxytocin and its analogues as potential future drug candidates for the treatment of AD would be an attractive and promising approach.