Page 9 - JCBP-1-2

Journal of Clinical and
Basic Psychosomatics Melatonin for dementia therapy

were detected in patients undergoing major liver resection causative factors in AD pathology ; therefore, melatonin
[41]
at doses up to 50 mg/kg . Therefore, melatonin could may play a role in slowing down AD progression through
[27]
possibly be used as a preventive and therapeutic agent for the regulation of NMDA receptors.
dementia. Extracellular signal-regulated kinase (ERK), which is
Melatonin inhibits dopamine release from areas such largely involved in neuronal plasticity and neuronal cell
[28]
as hypothalamus and hippocampus . Through the death, is also involved in neuronal anti-inflammatory
prevention of dopamine release, melatonin administration pathways and some studies have shown that melatonin
[42]
exhibits dual properties of exacerbating symptoms and increases ERK expression through melatonin receptors .
[43]
protecting against neurodegenerative disease in patients Moreover, the previous studies have shown that MT2-
with Parkinson’s disease . It has been reported that mediated potentiation of ERK signaling may improve
[28]
melatonin suppresses the amphetamine-induced release memory impairment . Therefore, ERK-mediated anti-
[44]
of dopamine neurotransmitters and reduces α-synuclein inflammatory and antioxidant effects may be associated
[29]
overexpression . Furthermore, melatonin is suggested with dementia.
to modulate dopaminergic neurotransmission through AMK is thought to be primarily involved in the
another mechanism , and this dopamine regulation may expression of ERK and CaMKII . The previous
[30]
[45]
play a role in dementia, such as DLB. studies have reported that age-related activation of the
Calcium/calmodulin-dependent kinase II (CaMKII), kynurenine pathway leads to tryptophan depletion and a
[46]
which is a major postsynaptic protein at excitatory decrease in melatonin . However, AMK has been shown
synapses, is one of the Ca /calmodulin-dependent protein to upregulate its precursor, N1-acetyl-N2-formyl-5-
2+
[47]
kinases and is activated by calmodulin (CaM), which plays methoxykynuramine, in in vivo models of inflammation .
a pivotal role in Ca signal transduction. CaMKII plays AMK, which has stronger antioxidant and memory-
2+
a fundamental role in synaptic plasticity and long-term enhancing effects, is involved in the expression of ERK
potentiation, which are both closely related to learning and and CaMKII, and, thus, may play a fundamental role in
memory in the central nervous system . In addition, the dementia.
[31]
previous studies have suggested that the CaMKII is involved It is generally accepted that melatonin improves sleep
in α-synuclein aggregation, which has been implicated in disorders and poor sleep quality through the regulation
DLB and Parkinson’s disease, and the proteasome, which of circadian rhythm and may also reduce sleep-related
is a protein degradation system [32,33] . It has been reported breathing disorders and their complications during
that melatonin binds tightly to CaM and acts as a CaM sleep . Because sleep apnea syndrome is involved in
[48]
antagonist . Interestingly, AMK works similarly to heart inflammation and hypertension , it is possible
[34]
[49]
melatonin, suggesting that many of the in vivo effects of that improved breathing during sleep through melatonin
melatonin may actually be mediated by AMK . However, administration may be related to improvements in
[35]
some studies have shown that melatonin decreases dementia and BPSD. Endogenous melatonin levels begin
CaMKII activity in lipidic microenvironments and to increase 2 h before sleep onset and help to promote sleep
increases CaMKII activity in aqueous microenvironments, through MT1/MT2 receptors . Furthermore, exogenous
[50]
suggesting that a more complex interaction between melatonin easily crosses the blood–brain barrier and, thus,
melatonin and CaMKII may exist . CaMKII and plays an important role in the treatment of insomnia.
[36]
melatonin are associated with memory formation , and Therefore, melatonin is an effective treatment for insomnia
[21]
both have been implicated in dementia and Parkinson’s caused by dementia. Furthermore, it is suggested that
disease [32,37] . There are some reports stating that the melatonin functions to remove amyloid-β, which leads to
regulation of CaMKII by melatonin inhibits α-synuclein “brainwashing,” and enhances sleep through the clearance
aggregation through the proteasome , and melatonin may of amyloid-β from the central nerve system, thus acting as a
[27]
also attenuate α-synuclein aggregation through pathways prophylactic agent against AD . In addition, some studies
[51]
involved in autophagy . Hence, the association between reported that phosphorylation of CaMKII affects sleep in
[38]
melatonin and CaMKII may be significant in improving rats ,while ERK has been shown to prepare the brain for
[50]
dementia-related symptoms. sleep in mice . Thus, it is suggested that melatonin’s effect
[49]
Studies have shown that melatonin increases NMDA on sleep may be related to CaMKII and ERK.
receptors in the rat hippocampus , and the modulation Melatonin has been suggested to have antidepressant and
[39]
of NMDA receptors leads to reactive oxygen species (ROS) anxiolytic effects and reportedly ameliorates anxiety and
reduction in ovariectomized rats . An insufficiency of depression-like behavior through the ventral hippocampus
[40]
NMDA receptors is also suggested to be one of the major in AD mice . Furthermore, melatonin receptors
[52]
Volume 1 Issue 2 (2023) 3 https://doi.org/10.36922/jcbp.1174