Md. Sahab Uddin

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

Neuroprotective Activity of Asparagus racemosus Linn. Against Ethanol-Induced Cognitive Impairment and Oxidative Stress in Rats Brain:Auspicious for Controlling the Risk of Alzheimer's Disease

Background: Medicinal plants are superior gift of nature to human lives to support disease free healthy life. Neurodegenerative diseases especially Alzheimer’s disease (AD) affects the central nervous system causing progressive degeneration of neurons, which affect cognitive function. The plant Asparagus racemosus (AR) Linn. has been used traditionally by Ayurvedic practitioners for nervous disorders. In this consequence, the intention of this study was to evaluate the neuroprotective effects of ethanolic extract of Asparagus racemosus (EEAR) Linn. roots in ethanol-induced cognitive impairment and oxidative stress in rats brain. Methods: The learning and memory enhancing activity of EEAR roots extract were investigated in Swiss albino male rats for 21 days and its effects on learning and memory were examined using various behavioral studies such as elevated plus maze (EPM) test, passive avoidance (PA) test, morris water maze (MWM) test, novel object recognition (NOR) test and biochemical studies such as lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity. Results: In the EPM test, administration of EEAR (i.e., 100 and 200 mg/kg b.w.) significantly (P<0.05, P<0.01) decreased retention transfer latency (RTL) on 21st day with respect to the disease control group. EEAR at 200 mg/kg b.w. markedly (P<0.05, P<0.01) increased the retention latency (RL) on 11th and 21st day compared to disease control group for PA test. In the NOR test administration of EEAR (i.e., 200 mg/kg b.w.) considerably (P<0.05) increased DI of rats on 21st day with respect to disease control group. Both doses of EEAR (i.e., 100 and 200 mg/kg b.w.) markedly (P<0.05, P<0.01) decreased escape latency (EL) and highest dose of EEAR (i.e., 200 mg/kg b.w.) noticeably (P<0.05, P<0.001) increased time spent in the target quadrant (TSTQ) on successive days for acquisition trial of MWM test. In case of probe trial administration of EEAR (i.e., 200 mg/kg b.w.) considerably (P<0.05, P<0.01) increased TSTQ and TSA (time spent in the annuli) of rats as compared to that of disease control group. EEAR administration (i.e., 100 and 200 mg/kg b.w.) significantly (P<0.01) decreased the TBARS level in the brain tissue of rats with respect to disease control group. The lowest and highest dose of EEAR (i.e., 100 and 200 mg/kg b.w.) significantly (P<0.05, P<0.01) decreases the AChE activity in the brain tissue of rats as compared to disease control group. Conclusion: The existing study displays that EEAR roots possesses an outstanding source for natural nootropic and confirming the traditional uses of this plant which could be industrialized for enhancing learning and memory impairment associated with neurodegenerative disorders particularly AD.

Exploring the Effect of Phyllanthus emblica L. on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in Rats: Promising Natural Gift for the Mitigation of Alzheimer's Disease

Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimers disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat. The effects of EEPEr and EEPEu fruits (i.e., 100 and 200 mg/kg b.w.) were examined in Swiss albino male rats for 12 days and its effect on cognitive functions, brain antioxidant enzymes, and AChE activity determined. Learning and memory enhancing activity of EEPE fruit was examined by using passive avoidance test and rewarded alternation test. Antioxidant potentiality was evaluated by measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase, reduced glutathione (GSH), glutathione-S-transferase, and the contents of thiobarbituric acid reactive substances (TBARS) in entire brain tissue homogenates. AChE activity was determined using colorimetric method. Administration of the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.01) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.05, p < 0.001) increased step-through latency in rats on 6th, 11th, and 12th day with respect to the control group. For aforementioned doses, the percentage of memory retention (MR) was considerably (p < 0.05, p < 0.01) increased in rats on 10th, 11th, and 12th days with respect to the control group. The extract, particularly highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit markedly (p < 0.05) and lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit significantly (p < 0.01) increased the correct responses in rats on 6th, and 12th day related to the control group. In case of this test, the percentage of MR was significantly (p < 0.05, p < 0.01) increased in rats treated with aforementioned doses on 12th day with respect to the control group. The highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit suggestively (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit suggestively (p < 0.05, p < 0.01, p < 0.001) increased the levels of SOD, CAT, GSH, GSH-Px and expressively (p < 0.01) decreased the TBARS level compared to the control group. Treatment with the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.01, p < 0.001) decreased the level of AChE activity compared to that of the control group. The present study shows that EEPE fruit possesses an excellent source for natural cognitive enhancer which could be developed in the treatment of AD and other neurodegenerative diseases.

Neurodefensive Effect of Olea europaea L. in Alloxan-Induced Cognitive Dysfunction and Brain Tissue Oxidative Stress in Mice: Incredible NaturalNootropic

Background: In the controlling of Alzheimer disease (AD) plant with antioxidant activity has attained considerable attention. The plant Oleaeuropaea (OE) L. belong to family Oleaceae is a rich source of natural antioxidant. Therefore the intention of this study was to analyze the neuroprotective effects of ethanolic extract of OE (EEOE) fruits in alloxan-induced cognitive impairment and brain tissue oxidative stress in mice by using Hole Cross (HC) test, Open Field (OF) test, Free Exploration (FE) test, Y-Maze (YM) test and contents of thiobarbituric acid reactivesubstances(TBARS)in braintissuehomogenates of mice. Methods: EEEO fruits were administered to alloxan-induced mice for 21st days. The neuroprotective effects ofthis fruit extracts were examined by using behavioral studies such as HC test, OF test, FE test, YM test and biochemical study such as lipid peroxidation (TBARS) assay. Results: In HC test, administration of EEOE on 14th and 21st day was remarkably (P < 0.05, P < 0.01) increased the number of hole crossed from one chamber to another by mice as compared to the disease control group. Administration of EEOE significantly (P < 0.01) increased the number of square travelled by mice on 21st day with respect to that of disease control group in OF test. In FE test EEOE considerably (P < 0.05, P < 0.01) increased the number of entries to the novel area and time spent in the novel area of the mice on 7th, 14th and 21st day as compared to the disease control group. The administration of EEOE significantly (P < 0.05, P < 0.01) increased the percentage of spontaneous alternation behavior of the mice on 14th and 21st day as compared to that of disease control group in YM test. EEOE administration for successive days markedly (P < 0.05) decreased TBARS level in the brain tissue homogenates of mice with respect to disease control group. Conclusion: The existing study suggests that EEOE fruit shows momentous neurodefensive activity. Consequently, this fruit extract may have impending therapeutic value in the treatment of some neurological disorders alike 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.

Analyzing the chance of developing dementia among geriatric people: a cross-sectional pilot study in Bangladesh: Analyzing the chance of dementia

Alzheimers disease is the most common form of dementia, representing 60–80% of cases, and ageing is the primary risk factor for the development of Alzheimers disease. The objective of this study was to examine the chance of developing dementia (i.e. mild cognitive impairment (MCI), Alzheimers disease) among geriatric people in Bangladesh.

APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis

Alzheimer’s disease (AD) is an immutable neurodegenerative disease featured by the two hallmark brain pathologies that are the extracellular amyloid ß (Aß) and intraneuronal tau protein. People carrying the APOE4 allele are at high risk of AD concerning the ones carrying the ε3 allele, while the ε2 allele abates risk. ApoE isoforms exert a central role in controlling the transport of brain lipid, neuronal signaling, mitochondrial function, glucose metabolism, and neuroinflammation. Regardless of widespread indispensable studies, the appropriate function of APOE in AD etiology stays ambiguous. Existing proof recommends that the disparate outcomes of ApoE isoforms on Aβ accretion and clearance have a distinct function in AD pathogenesis. ApoE–lipoproteins combine diverse cell-surface receptors to transport lipids and moreover to lipophilic Aβ peptide, that is believed to begin deadly events that generate neurodegeneration in the AD. ApoE has great influence in tau pathogenesis, tau-mediated neurodegeneration, and neuroinflammation, as well as α-synucleinopathy, lipid metabolism, and synaptic plasticity despite the presence of Aβ pathology. ApoE4 shows the deleterious effect for AD while the lack of ApoE4 is defensive. Therapeutic strategies primarily depend on APOE suggest to lessen the noxious effects of ApoE4 and reestablish the protective aptitudes of ApoE. This appraisal represents the critical interactions of APOE and AD pathology, existing facts on ApoE levels in the central nervous system (CNS), and the credible active stratagems for AD therapy by aiming ApoE. This review also highlighted utmost ApoE targeting therapeutic tactics that are crucial for controlling Alzheimer’s pathogenesis.

Neurochemistry of Neurochemicals: Messengers of Brain Functions

Neurochemistry refers to the chemical processes that occur in the brain and nervous system. This section of study determines how neurochemicals influence the network of neural operation. The brain transfers numerous chemical information via neurons to communicate. The main role of neurochemistry activities takes place in the brain, which allows it to perform numerous actions. Foundation of brain is a little bit different from man to man and several things can play a role in the levels of various neurotransmitters in the brain. It is supposed that differences in brain chemistry may accountable for a variety of behavioral disorders. A particular cell called neurons is the basis of brain. Neurotransmitters have the capability that it can trigger when ordered to do so, along with receptors for specific neurotransmitters. By sending messages with neurotransmitters to signal various cell activities, brain perform its functions. Neurotransmitter spreads chemical messages from neuron to neuron to broadcast certain work and thus it works. A neuron may accept many chemical messages, both positive and negative from the other neurons contiguous it. They are accountable to get the neuron to reply in different ways, or they may work combine to produce a certain effect. Since all of this occurs just within a split second, the neurotransmitter must be cleared away rapidly so that the same receptors can be activated again and again. Psychoactive drugs work by briefly influencing a mans neurochemistry, which thusly causes changes in a mans mind-set, cognition, perception and behavior. Neuropeptides are endogenous protein molecules that are utilized for neuronal signaling. These molecules exert more prolonged and diverse effects on behavior than neurotransmitters. Therefore the objective of this appraisal is to show study of the brain’s chemical makeup especially neurotransmitters, psychopharmaceuticals, neuropeptides and their activities to nervous tissue.

The Secret Linkage Amid Sugar and Heart Disease: Is Sugar Truly Foe Rather thanJust Friend?

Sugar is the crucial cradle of sweetness that embodies a prompt energy boost. It is something that we intake relentlessly and toils to precisely estimate sugar content in diet and food stuff because of its rife distribution [1]. Numerous studies advocated the occurrence of high amounts of added sugars up to 75% of all foods and beverages [2,3]. Owing to the arrival of modern food-processing methods, nowadays added sugar is a significant factor of the human diet. The endorsement for the intake of added sugar is not fixed yet it differs substantively. The World Health Organization praises that added sugar is accountable for less than 10% of total calories and as per Institute of Medicine it is less than 25% [4,5].

Study on Self-medication Practices among University Students of Bangladesh.

Aims: To know how much knowledge and awareness university students of Bangladesh have about commonly used medicines. Study Design: The study was conducted on 1200 students randomly selected from 9 university of Bangladesh, in which 87.5% were master’s student and remaining 12.5% were honor’s students. Each willing participant shared their opinion. Place and Duration of Study: Dhaka University (DU), Jahangirnagar University (JU), Eastern University (EU), East West University (EWU), Daffodil International University (DIU), North South University (NSU), International Islamic University Chittagong (IIUC), University of Information Technology & Science (UITS) and University of Science & Technology (USTC), Bangladesh, from May to July 2012. Methodology: Questionnaires were distributed among the students, information about students and knowledge about self-medication practices of medicine was determined. Results: The present study revealed that most frequently used medicine was analgesic/antipyretic Original Research Article Idris et al.; BJMMR, 14(6): 1-8, 2016; Article no.BJMMR.24364 2 (58.75%), followed by antiulcerants (40.17%), antibiotics (18.17%), antihistamines (10.58%) and antitussive (9.33%). 54.5% students took analgesic/antipyretic based on self-decision, followed by 49.83% antibiotics, 43.5% antiulcerants, 46.83% antitussives and 31.08% antihistamines respectively. Based on retailer advice 25% students took antimicrobials. 47.83% students said that they took antibiotics because of fever, 27% said the reason was infection, 13.58% took antibiotics because of GI disease and 12.5% mentioned others. 67.67% had no idea about side effect of antibiotics, followed by 53.17% for analgesic/antipyretic, 53.2% for antihistamine, 47.75% for antitussives and 28% for antiulcerants. Conclusion: Self-medication was practiced with a range of drugs from the analgesic/antipyretic to antibiotics. Most of the students didn’t know about the side-effects of these medicines as well as the antibiotics resistance. Although the practice of self-medication is unavoidable; drug authorities and health professionals need to educate students about the health hazards of self-medication.