Exploring the Anti-Neuroinflammatory Potential of Steroid and Terpenoid-Derived Phytochemicals to Combat Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that significantly affects cognitive functions in a way that causes loss of memory, thinking, and behavior. Multiple studies revealed that neuroinflammation associated with AD is linked with the amyloid-beta deposition in the brain. Elevated levels of expression of cytokines, microglial activation, nuclear factor kappa B, and reactive oxygen species play roles in AD-related inflammatory processes. Indeed, effective therapeutic approaches are urgently required to develop therapeutic agents to prevent and treat AD. So far, many anti-AD drug candidates have failed in the clinical stages and currently available drugs only provide symptomatic treatment. In recent times, pharmacologically active phytochemicals have been found to possess promising anti-neuroinflammatory effects; therefore, these natural products can be useful in AD treatment. In this review, we have comprehensively discussed the role of neuroinflammation and the molecular processes altered by multiple steroid and terpenoid-derived phytochemicals in various AD-related neuroinflammatory pathways. Indeed, steroid and terpenoid-derived phytochemicals show important therapeutic activities, which can be useful in ameliorating and treating AD-related neurodegeneration.

Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, which is progressively affecting elderly people. The dyshomeostasis of biometals and accumulation of toxic metals are usually observed in numerous neurodegenerative diseases including AD. In the central nervous system, metal imbalance-caused neurotoxic activities are usually linked with decreased enzymatic activities, increased aggregation of proteins, and oxidative stress, where a series of processes can result in neurodegeneration and cell death. Even though the relations between neurodegenerative diseases and biometal imbalance are still elusive, there is a growing interest in a group of major endogenous proteins that are associated with the transports of metals. Aberrant expression of these endogenous proteins is associated with the biometal imbalance and AD pathogenesis. Indeed, heavy metals are extremely toxic to the nervous system. Various studies have demonstrated that the toxic effects of heavy metals can result in amyloid beta (Aß) aggregation, neurofibrillary tangles, and even loss of neurons. In this article, we have focused on the molecular processes through which exposure to biometals and toxic metals can play roles in AD pathogenesis.

Molecular Insight into the Crosstalk of UPS Components and Alzheimer's Disease.

The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degradation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclusions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegeneration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.

Molecular Insight into the Therapeutic Promise of Targeting APOE4 for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes chronic cognitive dysfunction. Most of the AD cases are late onset, and the apolipoprotein E (APOE) isoform is a key genetic risk factor. The APOE gene has 3 key alleles in humans including APOE2, APOE3, and APOE4. Among them, APOE4 is the most potent genetic risk factor for late-onset AD (LOAD), while APOE2 has a defensive effect. Research data suggest that APOE4 leads to the pathogenesis of AD through various processes such as accelerated beta-amyloid aggregations that raised neurofibrillary tangle formation, cerebrovascular diseases, aggravated neuroinflammation, and synaptic loss. However, the precise mode of actions regarding in what way APOE4 leads to AD pathology remains unclear. Since APOE contributes to several pathological pathways of AD, targeting APOE4 might serve as a promising strategy for the development of novel drugs to combat AD. In this review, we focus on the recent studies about APOE4-targeted therapeutic strategies that have been advanced in animal models and are being prepared for use in humans for the management of AD.

Spectrum of Disease and Prescription Pattern for Outpatients with Neurological Disorders: An Empirical Pilot Study in Bangladesh.

BACKGROUND: Neurological disorders represent one of the most prominent causes of morbidity and mortality that adversely affect the lifestyle of patients and a major percentage of these diseases exists in developing countries. PURPOSE: The objective of this study was to examine the prevalence and prescription pattern for outpatients with neurological disorders in Bangladesh. METHODS: The study was conducted on 1,684 patients in 6 hospitals (National Institute of Neurosciences and Hospital, Dhaka Medical College and Hospital, Bangabandhu Sheikh Mujib Medical University, Shaheed Suhrawardy Medical College, Sir Salimullah Medical College, and Apollo Hospitals Dhaka) of the Dhaka City from March 2014 to June 2015. Data were collected through a predesigned questionnaire from the patients that contain information about gender, age, marital status, occupation, residential status, affected disease, self-medicated medicines, and prescribed medicines. RESULTS: Out of 1,684 patients, 28.38% patients were aged 51-60 years and male, 57.19% predominance. The study exposed headache and migraine for 29.75% patients, followed by stroke for 23.93% patients and seizure for 7.07% patients. Genetic reason for the neurological disorders was seen only among 12.35% patients. In this study, 16.98% patients had been affected by neurological disorders for more than 2 years and 19% of patients for less than 6 months. Most extensively prescribed medicines were multivitamins and multiminerals used by 17.89% of patients followed by nonsteroidal anti-inflammatory drugs and other analgesic by 14.84%; afterwards antiulcerants were used by 12.62%, subsequently anticoagulants were used by 11.61% followed by antihyperlipidemic medicines by 10.26% and antiepileptic drugs by 8.08% of patients. The crucial reasons for the selection of prescribed medicines were the confidence that patients had with the physician's prescribed medicines, which was shown for 40.97% patients and knowledge of the medicines was reported for 35.04% patients. The period of prescribed medicine usage was 1-3 months for 39.73% patients and 3-6 months for 29.16% patients. The patient's compliance for prescribed medicines was satisfactory for 34.56% patients, good for 28.15% patients, and side effects were reported for 23.22% patients. CONCLUSION: In Bangladesh, it is not surprising to note that neurological diseases are more prevalent than other different diseases among different age groups and genders. Headache and migraine, stroke and seizure are most frequently encountered neurological disorders here. Treatment procedure of these disorders is not quite suitable due to the anomalies of health care management systems. Appropriate management of the health care system, especially the placement of hospital and community pharmacy can overcome the existing inconsistencies as well as increase the knowledge, awareness, and perception of the patients about health and neurological disorders.