Role of melatonin in Alzheimer's disease: From preclinical studies to novel melatonin-based therapies.

Melatonin and novel melatonin-based therapies such as melatonin-containing hybrid molecules, melatonin analogues, and melatonin derivatives have been investigated as potential therapeutics against Alzheimer's disease (AD) pathogenesis. In this review, we examine the developmental trends of melatonin therapies for AD from 1997 to 2021. We then highlight the neuroprotective mechanisms of melatonin therapy derived from preclinical studies. These mechanisms include the alleviation of amyloid-related burden, neurofibrillary tangle accumulation, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and impaired neuroplasticity and neurotransmission. We further illustrate the beneficial effects of melatonin on behavior in animal models of AD. Next, we discuss the clinical effects of melatonin on sleep, cognition, behavior, psychiatric symptoms, electroencephalography findings, and molecular biomarkers in patients with mild cognitive impairment and AD. We then explore the effectiveness of novel melatonin-based therapies. Lastly, we discuss the limitations of current melatonin therapies for AD and suggest two emerging research themes for future study.

Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.

Relationships between Mitochondrial Dysfunction and Neurotransmission Failure in Alzheimer's Disease.

Besides extracellular deposition of amyloid beta and formation of phosphorylated tau in the brains of patients with Alzheimer's disease (AD), the pathogenesis of AD is also thought to involve mitochondrial dysfunctions and altered neurotransmission systems. However, none of these components can describe the diverse cognitive, behavioural, and psychiatric symptoms of AD without the pathologies interacting with one another. The purpose of this review is to understand the relationships between mitochondrial and neurotransmission dysfunctions in terms of (1) how mitochondrial alterations affect cholinergic and monoaminergic systems via disruption of energy metabolism, oxidative stress, and apoptosis; and (2) how different neurotransmission systems drive mitochondrial dysfunction via increasing amyloid beta internalisation, oxidative stress, disruption of mitochondrial permeabilisation, and mitochondrial trafficking. All these interactions are separately discussed in terms of neurotransmission systems. The association of mitochondrial dysfunctions with alterations in dopamine, norepinephrine, and histamine is the prospective goal in this research field. By unfolding the complex interactions surrounding mitochondrial dysfunction in AD, we can better develop potential treatments to delay, prevent, or cure this devastating disease.

New Directions in Pediatric Palliative Care Education for Preclinical Medical and Nursing Students.

OBJECTIVES: Since insufficient education has partially contributed to challenges in providing pediatric palliative care (PPC), a cross-sectional questionnaire study was conducted to explore the knowledge, attitudes, and educational needs of preclinical medical and nursing students in Hong Kong. METHODS: Pretested self-administered 44-item questionnaires with written informed consent were distributed to 241 medical and nursing students at Li Ka Shing Faculty of Medicine, the University of Hong Kong, between February and March 2019. This questionnaire covered eleven categories related to participants' knowledge of and attitudes towards PPC. A convenience sampling method was used. Data analysis was performed with descriptive statistics, chi-squared, and Fisher's exact test. RESULTS: Only 38.3% of participants had heard of PPC before, but 73.5% advocated for its local commencement. A large number, with more in nursing, misunderstood fundamental palliative concepts and pain assessment methods. Many reported that undergraduate curricula should include PPC since they were not prepared to deal and cope with dying children. More medical students identified multidisciplinary approaches in PPC while less believed that they were mentally prepared to discuss death and dying. The majority indicated family as the final decision maker, even for teenage patients. Although a large proportion agreed that PPC should be delivered at home since the diagnosis of a life-limiting illness, only a few were aware of the suggested referral structure. CONCLUSIONS: Most healthcare students were supportive of PPC despite their limited exposure. PPC education on palliative principles, pain management, multidisciplinary approaches, and emotional coping skills is needed and welcomed among students.