Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive function deficits. There are two major pathological hallmarks that contribute to the pathogenesis of AD which are the presence of extracellular amyloid plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Despite extensive research that has been done on Aβ in the last two decades, therapies targeting Aβ were not very fruitful at treating AD as the efficacy of Aβ therapies observed in animal models is not reflected in human clinical trials. Hence, tau-directed therapies have received tremendous attention as the potential treatments for AD. Tauopathies are closely correlated with dementia and immunotherapy has been effective at reducing tau pathology and improving cognitive deficits in animal models. Thus, in this review article, we discussed the pathological mechanism of tau proteins, the key factors contributing to tauopathies, and therapeutic approaches for tauopathies in AD based on the recent progress in tau-based research.
Melatonin, through its different receptors, has pleiotropic functions in mammalian brain. Melatonin is secreted mainly by the pineal gland and exerts its effects via receptor-mediated and non-receptor-mediated actions. With recent advancement in neuroanatomical mapping, we may now understand better the localizations of the two G protein-coupled melatonin receptors MT1 and MT2. The abundance of these melatonin receptors in respective brain regions suggests that receptor-mediated actions of melatonin might play crucial roles in the functions of central nervous system. Hence, this review aims to summarize the distribution of melatonin receptors in the brain and to discuss the putative functions of melatonin in the retina, cerebral cortex, reticular thalamic nucleus, habenula, hypothalamus, pituitary gland, periaqueductal gray, dorsal raphe nucleus, midbrain and cerebellum. Studies on melatonin receptors in the brain are important because cumulative evidence has pointed out that melatonin receptors not only play important physiological roles in sleep, anxiety, pain and circadian rhythm, but might also be involved in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Huntington's disease.
BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird’s nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.MethodsEBN was first prepared into pancreatin-digested crude extract and water extract. In vitro PD model was generated by exposing SH-SY5Y cells to neurotoxin 6-hydroxydopamine (6-OHDA). Cytotoxicity of the extracts on SH-SY5Y cells was tested using MTT assay. Then, microscopic morphological and nuclear examination, cell viability test and ROS assay were performed to assess the protective effect of EBN extracts against 6-OHDA-induced cellular injury. Apoptotic event was later analysed with Annexin V-propidium iodide flow cytometry. To understand whether the mechanism underlying the neuroprotective effect of EBN was mediated via mitochondrial or caspase-dependent pathway, mitochondrial membrane potential (MMP) measurement and caspase-3 quantification were carried out.ResultsCytotoxicity results showed that crude EBN extract did not cause SH-SY5Y cell death at concentrations up to 75 μg/ml while the maximum non-toxic dose (MNTD) of water extract was double of that of crude extract. Morphological observation and nuclear staining suggested that EBN treatment reduced the level of 6-OHDA-induced apoptotic changes in SH-SY5Y cells. MTT study further confirmed that cell viability was better improved with crude EBN extract. However, water extract exhibited higher efficacy in ameliorating ROS build up, early apoptotic membrane phosphatidylserine externalization as well as inhibition of caspase-3 cleavage. None of the EBN treatment had any effect on MMP.ConclusionsCurrent findings suggest that EBN extracts might confer neuroprotective effect against 6-OHDA-induced degeneration of dopaminergic neurons, particularly through inhibition of apoptosis. Thus EBN may be a viable nutraceutical option to protect against oxidative stress-related neurodegenerative disorders such as PD.
BACKGROUND: Polypharmacy is associated with the increased use of potentially inappropriate medications, where the risks of medicine use outweigh its benefits. Stopping medicines (deprescribing) that are no longer needed can be beneficial to reduce the risk of adverse events. We summarized the willingness of patients and their caregivers towards deprescribing. METHODS: A systematic search was conducted in four databases from inception until April 30, 2021 as well as search of citation of included articles. Studies that reported patients' and/or their caregivers' attitude towards deprescribing quantitatively were included. All studies were independently screened, reviewed, and data extracted in duplicates. Patients and caregivers willingness to deprescribe their regular medication was pooled using random effects meta-analysis of proportions. RESULTS: Twenty-nine unique studies involving 11,049 participants were included. All studies focused on the attitude of the patients towards deprescribing, and 7 studies included caregivers' perspective. Overall, 87.6% (95% CI: 83.3 to 91.4%) patients were willing to deprescribe their medication, based upon the doctors' suggestions. This was lower among caregivers, with only 74.8% (49.8% to 93.8%) willing to deprescribe their care recipients' medications. Patients' or caregivers' willingness to deprescribe were not influenced by study location, study population, or the number of medications they took. DISCUSSION: Most patients and their caregivers were willing to deprescribe their medications, whenever possible and thus should be offered a trial of deprescribing. Nevertheless, as these tools have a poor predictive ability, patients and their caregivers should be engaged during the deprescribing process to ensure that the values and opinions are heard, which would ultimately improve patient safety. In terms of limitation, as not all studies may published the methods and results of measurement they used, this may impact the methodological quality and thus our findings.
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