Page 8 - JCBP-1-2

Journal of Clinical and
Basic Psychosomatics Melatonin for dementia therapy

are administered to promote neuroprotection, suppress it is necessary to improve ameliorating drugs that act
acetylcholine degradation, and improve memory against the functional deterioration of the proteasome and
impairment . autophagy and prevent the accumulation of denatured
[2]
Common symptoms of VaD include apathy, depressive proteins due to aging or other factors.
symptoms, and memory impairment, similar to AD In addition to the core symptoms of dementia, such
symptoms. VaD is caused by neuronal cell death and partial as memory impairment, lack of judgment, and agnosia,
loss of function due to various vascular disorders, such as behavioral and psychological symptoms of dementia
cerebral infarction and cerebral hemorrhage, and is also (BPSD) may occur, which result in sleep disorders,
correlated with transient ischemic attacks, hypertension, depression, anxiety, delusions, and visual hallucinations.
and hyperlipidemia . VaD is a common condition for BPSD imposes a great physical and psychological burden,
[3]
which there are currently no specific treatments because the not only on the patient but also on the caregiver. Sleep
underlying pathology is still unclear. However, medications disorder, one of the BPSD, contributes to a decline in
that improve cerebral circulation and metabolism, such as cognitive function and an increased risk of dementia .
[9]
nicergoline, antihypertensive drugs, and therapeutics, are Some studies showed that the expression deficiency of
the currently available medications used to improve the Bmal1, a circadian clock gene, is an important contributor
symptoms of AD [4,5] . to aging-related diseases such as AD and that Bmal1
expression is also attenuated with aging . Thus, substantial
[10]
Excessive aggregation of α-synuclein is the purported
primary cause of DLB, which is similar to Parkinson’s attention and care are required for ameliorating BPSD.
disease. DLB is characterized by an α-synuclein-mediated 2. Melatonin activity for improving dementia
blockage of dopamine release, particularly from the
substantia nigra to the striatum, leading to amnesia, visual In the central nervous system, melatonin, which
hallucinations, and delusions. Cholinesterase inhibitors is synthesized and secreted from the pineal gland,
and NMDA inhibitors are used in the same way as in AD, is mediated by the G-protein-coupled melatonin
and levodopa, a dopamine action enhancer that is also receptors, MT1/MT2, and is known to regulate circadian
used as a therapeutic agent for Parkinson’s disease, is used rhythm, seasonal reproduction, and plays a role in
to treat DLB in some cases . thermoregulation [11-14] . In addition, melatonin has been
[6]
reported to exert receptor-mediated and non-receptor-
In FTD, decreased progranulin enhances the excessive mediated antioxidant and anti-inflammatory effects [15-18] .
phosphorylation of tau, and abnormally, aggregated tau is Some studies have reported that melatonin may be partly
thought to cause neuronal cell death due to symptoms of related to the modulation of apoptosis and protection of
dementia. However, it should be noted that there are also the cholinergic system, which is associated with AD .
[19]
non-tau forms of FTD and that FTD is a neuropathologically Recently, it has been revealed that a single dose of melatonin
and genetically diverse condition. FTD can be divided into enhances learning and memory functions, and that short-
two main categories: (i) the behavioral variant of FTD with term and long-term memory enhancement is mediated
changes in social behavior and personality, and (ii) primary by melatonin and N1-Acetyl-5-methoxykynuramine
progressive aphasias with gradual loss of language skills (AMK), which is a melatonin metabolite known to act
from the early stages. FTD is characterized by obsessive- as an antioxidant against free radicals [20-22] . Research has
compulsive repetitive behavior, hoarding behavior, anti- shown that the long-term administration of melatonin
social behavior and lack of empathy in the behavioral may attenuate memory deficits caused by aging through
variant, and difficulty remembering common words its antioxidant and anti-inflammatory effects [23-25] . These
and poor word comprehension in primary progressive neuroprotective effects may also prevent the development
[7]
aphasias . At present, there are no effective therapies for of dementia. Moreover, it has been reported that
these cognitive impairments.
melatonin may have sleep-promoting effects through the
Among these four common types of dementia, AD, regulation of circadian rhythm and could improve sleep
DLB, and FTD are classified as neurodegenerative diseases, disorders caused by BPSD [12,15,23] . Research has indicated
and VaD is classified as a non-neurodegenerative disease. that long-term administration of melatonin improves
Abnormal protein aggregation is associated with AD, DLB, cognitive performance, and single-dose administration of
and FTD, as well as a wide range of neurodegenerative melatonin enhances memory and may ameliorate memory
diseases, and developing treatments to inhibit protein impairment caused by dementia [12,20,21] . Furthermore,
aggregation has become increasingly necessary, and may melatonin has very minimal side effects that no acute
be useful in treating other diseases, such as polyglutamine toxicity was observed in mice that had been administered
disease and amyotrophic lateral sclerosis . Therefore, with doses of up to 800 mg/kg and no serious side effects
[8]
[26]
Volume 1 Issue 2 (2023) 2 https://doi.org/10.36922/jcbp.1174