Alzheimer's disease (AD) is the most common form of dementia, affecting millions of individuals each year and this number is expected to significantly increase. The complicated microorganisms residing in human gut are closely associated with our health. Emerging evidence has suggested possible involvement of human gut microbiome in AD. Symbiotic gut microbiomes are known to maintain brain health by modulating host's barriers integrity, metabolic system, immune system, nervous system and endocrine system. However, in the event of gut dysbiosis and barriers disruption, gut pathobionts disrupt homeostasis of the metabolic system, immune system, nervous system, and endocrine system, resulting in deterioration of neurological functions and subsequently promoting development of AD. Multiple therapeutic approaches, such as fecal microbiome transplant, antibiotics, prebiotics, probiotics, symbiotic, and diet are discussed as potential treatment options for AD by manipulating the gut microbiome to reverse pathological alteration in the systems above.
Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5'-adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.
The endosomal-lysosomal system mediates the process of protein degradation through endocytic pathway. This system consists of early endosomes, late endosomes, recycling endosomes and lysosomes. Each component in the endosomal-lysosomal system plays individual crucial role and they work concordantly to ensure protein degradation can be carried out functionally. Dysregulation in the endosomal-lysosomal system can contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). In AD endosomal-lysosomal abnormalities are the earliest pathological features to note and hence it is important to understand the involvement of endosomal-lysosomal dysfunction in the pathogenesis of AD. In-depth understanding of this dysfunction can allow development of new therapeutic intervention to prevent and treat AD.
Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer.
Diabetic neuropathy (DN) is a condition in which nerve fibers are continually exposed to high glucose-induced free radicals. Recent discoveries demonstrated that melatonin is an indole hormone that contributes to neuroprotection through the modulation of autophagy. Herein, this study aims to examine the neuroprotective effects of melatonin on Schwann cells under high glucose conditions. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was used to measure cell viability. The activation of autophagosomes was determined using acridine orange staining (AO). Western blot assay was used to measure the expression of proteins involved in autophagy and endoplasmic reticulum (ER) stress. Our results demonstrated that melatonin at 1 µM has the highest protective effects on high glucose-induced cell death. Melatonin concentrations of 5 and 10 µM were found to be the most effective in reducing autophagy induced by high glucose. Under high glucose conditions, the protein expressions of LC3, ATF4, ATF6, CHOP, PERK and eIF2-α were up-regulated in Schwann cells. However, melatonin attenuated these changes by downregulating LC3 and the ER stress markers ATF4, ATF6, CHOP, PERK and eIF2-α protein expressions in Schwann cells. In conclusion, melatonin alleviates high glucose-induced autophagy in Schwann cells through PERK-eIF2α-ATF4-CHOP signaling pathways.