Title:Melatonin Receptor as a Drug Target for Neuroprotection
Volume: 14
Author(s): Pawaris Wongprayoon and Piyarat Govitrapong*
Affiliation:
- Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, 10210,Thailand
Keywords:
Melatonin receptor, alzheimer's disease, parkinson's disease, neurodegeneration, neurogenesis, ischemic brain injury.
Abstract:
Background: Melatonin, a neurohormone secreted from the pineal gland, circulates
throughout the body and then mediates several physiological functions. The pharmacological effects
of melatonin can be mediated through its direct antioxidant activity and receptor-dependent
signaling.
Objective: This article will mainly review receptor-dependent signaling. Human melatonin receptors
include melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2), which are widely
distributed throughout the brain.
Result: Several lines of evidence have revealed the involvement of the melatonergic system in different
neurodegenerative diseases. Alzheimer’s disease pathology negatively affects the melatonergic
system. Melatonin effectively inhibits β-amyloid (Aβ) synthesis and fibril formation. These effects
are reversed by pharmacological melatonin receptor blockade. Reductions in MT1 and MT2 expression
in the amygdala and substantia nigra pars compacta have been reported in Parkinson’s disease
patients. The protective roles of melatonin against ischemic insults via its receptors have also
been demonstrated. Melatonin has been reported to enhance neurogenesis through MT2 activation
in cerebral ischemic/reperfusion mice. The neurogenic effects of melatonin on mesenchymal stem
cells are particularly mediated through MT2.
Conclusion: Understanding the roles of melatonin receptors in neuroprotection against diseases
may lead to the development of specific analogs with specificity and potency greater than those of
the original compound. These successfully developed compounds may serve as candidate preventive
and disease-modifying agents in the future.