Alzheimer?s disease: A Common Form of Neurodegeneration
Prabhat Shukla1*, and Neeru Tyagi1
1Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut, India
- Corresponding Author:
- Prabhat Shukla
Department of Pharmaceutical Technology
Meerut Institute of Engineering and Technology
E-mail: [email protected]
Received: 03/01/2015; Accepted: 04/02/2015; Published: 11/02/2015
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CNS, Neurodegenerative disease, Alzheimer's disease, Aging, Amyloid β-peptide, Reactive oxygen species
The human nervous system is an extremely complex structure, having billions of nerve cells or neurons . Central nervous system (CNS) is a vital organ system [2-4]. Nerve cells of the central nervous system rarely divides after differentiation . Neurodegeneration term refers to progressive loss of neurons. Alzheimer’s (AD) and Parkinson’s (PD) diseases are the most common neurodegenerative disorders in elders [6,7]. Progressive cell death in brain neuronal circuits occurs too often from brain injuries caused by diseases like Parkinson’s disease and Alzheimer’s disease . Alois Alzheimer reported the autopsy findings of the brain of a woman who died of dementia at the age of 55 in 1906. He explained a “peculiar severe disease process of the cerebral cortex” with “miliary foci” (β-amyloid plaques) and “fibrils” (neurofibrillary tangles). The condition was termed as “Alzheimer’s Disease” in 1910 in Kraepelin’s textbook of psychiatry. Alzheimer’s findings came into notice when the original histological slides were re-examined in 1998 using modern histochemical and genetic techniques [9,10]. Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders . Age is the most important aspect determining the incidence and prevalence of neurodegeneration , cognitive impairment and dementia [9,13,14]. In a cohort study in USA the age specific rates of all-cause of dementia increases from 4·85 per 1,000 people in 65-69 year’s age group to 84·19 per 1,000 people in 90+ year’s age group [9,15]. Social isolation appears to increase cognitive decline irrespective of AD pathology, and the harmful effects of AD pathology are minimized by social engagement [9,16]. The prevalence of AD doubles every 5 years, after the age of 65 years. Furthermore the prevalence of AD in Late onset alzheimer’s disease, in individuals over age 70, was found to be 2.3 million in 2002 .The prevalence of AD in patients of age 65 and above was 4.5 million in 2000 in U.S. The prevalence was latter updated to 5.3 million in 2008. The prevalence of AD in the world is estimated to be around 35.6 million in 2010.The number for the future are still exceeding with estimated 65 million in 2030 affected with AD and 115 million in 2050 affected with AD costing our global economy US$604 billion [17,18]. Perea RD, et al. suggested that individuals at early stages of Alzheimer’s dementia did not appear to have significant white matter degeneration compared to non-demented elderly subjects [13,19,20]. AD is characterized by intracellular neurofibrillary tangles, intra-neuronal accumulation of hyper-phosphorylated tau forms and extracellular amyloid β-peptide (Aβ) deposits contributing to senile plaques [11,15,21]. Aβ is responsible for senile plaques (SPs) and tau is responsible for neurofibrillary tangles (NFTs). But, the primary cause for AD is the deposition of Aβ . Aβ is a peptide which is a part of larger protein amyloid precursor protein (APP)  APP is a single-pass transmembrane protein with large extracellular domains. APP modulates cell growth, movement, neurite outgrowth, and cell survival [24,25]. The most important role of APP in the development of Alzheimer’s disease depends on the toxicity of the Aβ peptide. Aβ fibrils are acutely toxic to neurons resulting in cell death due to its oxidative effects [26-29]. Aβ generates the reactive oxygen species (ROS) which is responsible for neuron damage [30-34] as mutation of a single amino acid of the Aβ peptide eliminates its ability to generate ROS. Hugon J et al. reported that Aβ oligomers can lead to the production of TNFα [35,36] which causes memory impairment in mice and monkeys . Soluble Aβ also controls the cleavage and phosphorylation of tau, both of which are important for neurofibrillary tangle (NFT) generation . Neurofibrillary tangles composed of tau fibrils (NFTs) are an increasingly recognized part of the AD pathogenesis. Their intracellular formation around nerve endings signifies the extracellular accumulation of Aβ plaques. The fibrils of tau protein in AD brains are known as paired helical filament (PHFs) which is a structural form that tau proteins seem to aggregate in AD. Tau protein is surrounded by the Aβ protein in AD.[38-40]. Free radicals [41-43] are produced by the amyloid peptide once it is formed outside the neurons, and these free radicals were found to be neurotoxic to hippocampal cells and the synaptosomal membranes. These free radicals also damage the lipid membranes (lipid peroxidation) of the neurons leading to death [44-49]. Oxidative stress-inducing metal ions, such as iron (Fe), copper (Cu), zinc (Zn) and aluminum (Al) may contribute to the formation of SPs/NFTs and neuronal damage in the AD brain. Aluminium [50,51] is one of the major metal that cause free radical generation, giving Al phosphate injections into the brains of rabbits caused epilepsy and neurofibrillary changes [21,45,52]. Al is associated with the aggregation of Aβ and p-tau, and is also involved in Aβ deposition. So, due to free radical generating property of Al, it promotes cognitive impairment in rodents and humans [21,52]. Bastian et al. discussed the involvement of bacteria as a causal agent for the neurodegenerative diseases, and related the evidence to involvement of spiroplasma in the pathogenesis of the encephalopathy as a model for the neurodegenerative diseases (mainly AD) . Gardener et al., discussed the role of diet in the developement of neurodegenerative diseases. Diet plays a major role in the development of neurodegenerative diseases such as Alzheimer’s disease. There is increasing evidence that the components in the food that we consume, interacts with each other to impart disease protection and a higher level of health . According to Cholinergic hypothesis, AD is caused by reduced synthesis of Acetylcholine (neurotransmitter) [55-57], in this the AchE (acetylcholine esterase) levels were increased which causes damage to the cholinergic neurons finally leading to cognitive impairments [12,58].
Symptoms of AD
The most common symptom of AD is memory loss which worsens as the disease progresses. People with severe Alzheimer's cannot communicate and are completely dependent on others for their daily activities . It is characterized by loss of cognitive  and non-cognitive functions. Non-cognitive symptoms occur just before the onset of cognitive symptoms. Non-cognitive symptoms in AD include behavioural and neurological symptoms. Cognitive function refers to an individual’s perceptions, memory, thinking, social awareness and reasoning [17,60-62]. Cognitive decline includes multiple cognitive domains like decline in memory, orientation and executive functions. Depression and anxiety are common phenomena among patients with mild AD, whereas aggression, agitation, and apathy are more frequent in those patients at severe states of the disease . Field T et al. described the smell and taste as an early marker of neurodegenerative diseases. The etiology and development of these sensory dysfunctions are not known, but the involvement dopamine [64,65], norepinephrine, serotonin, acetylcholine and orbitofrontal [66,67] cortex systems have been suggested in several of the neurodegenerative and neuropsychiatric conditions associated with smell dysfunction [68-70].
The main problem in the treatment and management of AD is penetration in the blood brain barrier (BBB) [52,71]. Many research evidences suggest that various antioxidant therapies plays a major role in free radical scavenging and reduce oxidative stress, therefore they can be possible therapeutic options to treat AD [45,72,73]. Four major categories of drugs are used in AD treatment :
• cholinergic treatment
• anti-glutamatergic treatment
• vitamins and anti-oxidants
• nonsteroidal anti-inflammatory drugs (NSAIDs) [75,76]
Out of these Acetylcholinesterase inhibitors (AChEIs) are the main line treatment options. AChEIs increases the availability of acetylcholine and thus facilitating cholinergic neurotransmission which in turn have positive benefits on cognition. Donepezil hydrochloride [77-81] is an acetylcholinesterase inhibitor, which improves cognitive function by inhibiting the enzyme acetylcholinesterase and activates cholinergic neurons via an increase of acetylcholine . Blockade of glutamatergic neurotransmission by use of the uncompetitive N-methyl-D-aspartate (NMDA) antagonist (memantine)  subsequently blunts excitotoxicity, which is due to excess intracellular calcium, resulting in less generation of free radicals hence decreased neurodegeneration .
According to Bunik VI et al., transient improvement in cognitive function of patients with neurodegenerative diseases, including Alzheimer disease (AD) has been observed upon thiamin (vitamin B1) administration . Thiamin acts as a coenzyme of the enzymes of central metabolism [85-88]. Many drugs are available for the treatment of Alzheimer’s disease but, they only slow the neurodegenerative process and does not treat the disease , these usually treat the symptoms of the AD but cannot stop the progression of the disease. Also they have side effects such as dizziness, headache, constipation and confusion . There is growing evidence on the effectiveness of non-pharmacological and psycho-social interventions, such as individualised or group-based reminiscence therapies, joint reminiscence sessions with family members, and stimulating sensorial experiences for adults with dementia that helps in delaying the progression of the disease [18,90]. Yellamma K et al. suggested that Sericin (silk protein) in a dose of 200 mg/kg body weight have neuroprotective properties as it reverse the memory impairments in AD-induced rat .
How AD is Diagnosed in vitro?
In vitro study is done by the researchers to find out the novel therapeutic agents that can treat AD. There are various parameters that are studied during the pharmacological studies. These are of two types: biochemical and behavioural parameters [12,38].
These include estimation of acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH) [91-95].
Various parameters are involved in the determination of AD in rats. These include: Morris water maze test (Spacial learning) Passive avoidance paradigm (Memory) Locomotor activity by actophotometer Stair case test (Spatial recognition) etc [12,96]. These parameters in all helps in determining the extent of action of novel drugs and thus, helps in development of newer therapeutic agent.
Recent researches are in a process of developing new drugs like Edaravone. Developed by the scientists from the University of South Australia, Edaravone can alleviate the progressive cognitive deficits of Alzheimer's disease [97,98]. Edaravone binds to the toxic amyloid peptide which is a major factor leading to degeneration of nerve cells and suppresses its action. Edaravone can suppress the toxic functions of amyloid beta to nerve cells-it is a free radical scavenger which suppresses oxidative stress that is a main cause of brain degeneration. The drug can halt the production of amyloid beta by inhibiting the amyloid beta production enzyme. It also inhibits the hyperphosphorylation of Tau protein, which can generate tangles accumulated in the brain cells and damage brain functions . Secondly, a new drug AZD05030, developed by Astra Zeneca tends to block damage initiated during the formation of amyloid-beta plaques which is a distinctive feature of AD. In the experiment cells under bombardment by beta amyloid plaques show restored synaptic connections and reduced inflammation, and the animal's memory, which was lost during the course of the disease, is restored .
AD is one of the major causes of dementia in the elders and is the most common form of dementia  that affects an estimated 33.9 million people worldwide. It is the sixth leading cause of death in the US . Aging causes a slow but steady deterioration of the brain function leading to cognitive decline, memory loss, movement disorders and finally to functional decline and death . There are many therapeutic agent present for the treatment of neurodegenerative disorders but they and not effective is completely curing the disease. These drugs usually slow down the rate of degenerative process but, in the end the damage will lead to fatal situations. In recent researches, scientist claim to have a potent drug for treating the neurodegeneration but, fails to slow or halt the disease progression. These drugs include mainly the flavonoid class and other free radical scavenging agents [103-106].
Researchers are on a verge of finding novel drugs for the treatment of AD. Current drugs help in masking the symptoms of Alzheimer's, but do not treat the underlying disease or delay its progression. Advancement may be the drug that would treat the underlying disease and stop or delay the cell damage that eventually halt the worsening of symptoms.
- Jackson KL et al. Expanded Central Nervous System Gene Transfer in Rats by Intravenous Delivery of Recombinant Adeno-Associated Virus. J Neurol Disord. 2015;3:i109.
- Patil PJ et al. Central Nervous System (CNS) Activity of Argyreia speciosa and Acorus calamus: A Review. RRJPP. 2014;2:1-9.
- Devasena T and Francis AP. Nanotoxicity-Induced Alzheimer Disease and Parkinsonism: Not Further than Diagnosis. J Alzheimers Dis Parkinsonism. 2015;5:178.
- Denis PA. The Continuum of Metabolic Stress According to the Gas Model of Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:149.
- Sani M et al. Successful Regeneration of CNS Nerve Cells a Possible Bye Bye O Debilitating Effects Of Neurodegenerative Diseases. J Alzheimers Dis Parkinsonism. 2015;5:182.
- Ezza HSA and Khadrawyb YA. Glutamate Excitotoxicity and Neurodegeneration. J Mol Genet Med. 2014;8:141.
- Werner FM and Covenas R. Treatment of Psychotic Symptoms in Parkinson’s Disease. J Cytol Histol. 2015;6:e115.
- Saleem W and Broderick PA. Biomarkers for Brain Disorders Electrochemically Detected By BRODERICK PROBE® Microelectrodes/Biosensors. J Biosens Bioelectron. 2013;S12:003.
- Davey DA. Alzheimer’s Disease, Cerebrovascular Disease and Dementia: A Potentially Preventable and Modifiable Syndrome. J Alzheimers Dis Parkinsonism. 2015;5:184.
- Tsai A et al. Differences in Cerebrospinal Fluid Biomarkers between Clinically Diagnosed Idiopathic Normal Pressure Hydrocephalus and Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:150.
- Kumar A et al. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacological Reports. 2015;67:195-203.
- Utkin YN et al. What Animal Models of Parkinsonism Tell us About the Distinct Nicotinic Acetylcholine Receptors Involved in Pathogenesis? J Alzheimers Dis Parkinsonism. 2015;5:181.
- Perea RD et al. A Comparative White Matter Study with Parkinson’s disease, Parkinson’s Disease with Dementia and Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2013;3:123.
- Deacon RMJ. A Novel Approach to Discovering Treatments for Alzheimer’s Disease. J Alzheimers Dis Parkinsonism.2014;4:142.
- Ohyagi Y and Miyoshi K. Aluminum and Alzheimer’s Disease: An Update. J Alzheimers Dis Parkinsonism. 2013;3:118.
- Pallanti S and Marras A. Transcranial Magnetic Stimulation in Alzheimer’s Disease: A Review of Investigational and Therapeutic Findings. J Alzheimers Dis Parkinsonism. 2015;5:187.
- Mushtaq R et al. Comparison of Cognitive Symptoms in Subtypes of Alzheimer’s disease (AD)-a study from South East Asia (Kashmir, India). J Alzheimers Dis Parkinsonism. 2014;4:167.
- Park AL. Is There Anything Special About Intergenerational Approaches to Older People with Dementia? A Review. J Alzheimers Dis Parkinsonism. 2014;4:172.
- Maksimovskiy A et al. White Matter and Cognitive Changes in Veterans Diagnosed with Alcoholism and PTSD. J Alcoholism Drug Depend. 2013;2:144.
- Tsai SH et al. Age-related Changes of White Matter in the Elderly Population Measured by Diffusion Tensor Imaging. OMICS J Radiology. 2012;1:107.
- Godoy JA et al. SIRT1 Protects Dendrites, Mitochondria and Synapses from Aß Oligomers in Hippocampal Neurons. J Alzheimers Dis Parkinsonism. 2013;3:126.
- de Oliveira Lanna ME et al. Diabetes Effects in Alzheimer Disease: The Interactive Role of Insulin and Aß Peptide. J Alzheimers Dis Parkinsonism. 2013;4:151.
- Whitesman P. Preliminary Set Theory-Type Analysis of Proteins Associated With Parkinsonâ€™s Disease. J Alzheimers Dis Parkinsonism. 2014;4:170.
- Swerdlow RH. Pathogenesis of Alzheimer’s disease. Clin Interv Aging. 2007;2:347-359.
- O’Brien RJ and Wong PC. Amyloid Precursor Protein Processing and Alzheimer’s Disease. Annu Rev Neurosci. 2011;34:185-204.
- Lukiw WJ et al. Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer’s Disease (AD) . J Alzheimers Dis Parkinsonism. 2015;5:177.
- Komaravelli N and Casola A. Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses. J Pharmacogenomics Pharmacoproteomics. 2014;5:141.
- Boligon AA et al. Technical Evaluation of Antioxidant Activity. Med chem. 2014;4:517-522.
- Chamorro E et al. Photoprotective Effects of Blue Light Absorbing Filter against LED Light Exposure on Human Retinal Pigment Epithelial Cells In Vitro. J Carcinog Mutagen. 2013;S6:008.
- Kyle D Maxwell et al. The Plasmalemmal Na/K-ATPase: An Amplifier for Reactive Oxygen Species?. J Hypertens. 2015;4:197.
- Tamara Perchyonok V et al. Bioactive-Functionalized Interpenetrating Network Hydrogel (BIOF-IPN): A Novel Biomaterial Transforming the Mechanism of Bio-Repair, Bio-Adhesion and Therapeutic Capability â€“ An In Vitro Study. J Interdiscipl Med Dent Sci. 2015;3:166.
- Dallatu MK et al. The Role of Hypoxia-Inducible Factor/Prolyl Hydroxylation Pathway in Deoxycorticosterone Acetate/Salt Hypertension in the Rat. J Hypertens. 2014;3:184.
- Jung YG. Capital-Skill Complementarity and Jobless Recovery. J Stock Forex Trad. 2013;2:104.
- Dananjaya SHS et al. Chitosan Silver Nano Composites (Cagncs) as Potential Antibacterial Agent to Control Vibrio tapetis. J Veterinar Sci Technol. 2014;5:209.
- Lingbin Meng et al. Role of IL6 and TNFa in Hippocampal Neurogenesis of TAM Triple Knockout Mice. Int J Adv Innovat Thoughts Ideas. 2014;3:155.
- Nayak BN et al. Immune Modifiers from Selected Prairie Crops: Concentration Effects of Mixed Linkage (1→3, 1→4) ß-Glucans and Saskatoon Berry Extracts on TNF α Expression and Cell Growth in RAW264.7 Cells. J Nutr Food Sci. 2013;3:232.
- Hugon J et al. Involvement of PKR in Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:154.
- Shokouhi S et al. Imaging Brain Metabolism and Pathology in Alzheimer’s Disease with Positron Emission Tomography. J Alzheimers Dis Parkinsonism. 2014;4:143.
- Barz H et al. Neuronal Impulse Theory and Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:134.
- Borchelt RD et al. Proteostasis and Secondary Proteinopathy in Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:145.
- Madeo J and Elsayad C. The Role of Oxidative Stress in Alzheimerâ€™s Disease. J Alzheimers Dis Parkinsonism. 2013;3:116.
- Ezza HSA and Khadrawyb YA. Glutamate Excitotoxicity and Neurodegeneration. J Mol Genet Med. 2014;8:141.
- Neeti Sharma. Free Radicals, Antioxidants and Disease. Biol Med. 2014;6:214.
- Tuppo EE and Forman LJ. Free radical oxidative damage and Alzheimer’s disease. JAOA. 2001;101:S11-S15.
- Tiwari SC and Soni RM. Alzheimer’s Disease Pathology and Oxidative Stress: Possible Therapeutic Options. J Alzheimers Dis Parkinsonism. 2014;4:162.
- Lee S et al. CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2013;3:128.
- Meena Bai M et al. Evaluation of Genotoxic and Lipid Peroxidation Effect of Cadmium in Developing Chick Embryos. J Environ Anal Toxicol. 2014;4:238.
- Abbassy A et al.Impact of Oxidative Stress and Lipid Peroxidation Induced by Lambda-cyhalothrin on P450 in Male Rats: The Ameliorating Effect of Zinc. J Environ Anal Toxicol. 2014;4:218.
- Ragab AR et al. The Role of Oxidative Stress in Carcinogenesis Induced By Metals in Breast Cancer Egyptian Females Sample at Dakahlia Governorate. J Environ Anal Toxicol. 2014;4:207.
- Amjad S and Umesalma S. Protective Effect of Centella asiatica against Aluminium-Induced Neurotoxicity in Cerebral Cortex, Striatum, Hypothalamus and Hippocampus of Rat Brain-Histopathological, and Biochemical Approach. J Mol Biomark Diagn. 2015;6:212.
- Haas G et al. The Effect of Aluminium on the Morphologic Appearance, Viability and Phagocytic Activity of ARPE-19 Cells. J Clin Exp Ophthalmol. 2014;5:383.
- Abdulmalek S et al. Possible Neuroprotective Role of Pomegranate Juice in Aluminum Chloride Induced Alzheimerâ€™s Like Disease in Mice. J Alzheimers Dis Parkinsonism. 2015;5:188.
- Bastian FO. Cross-Roads in Research on Neurodegenerative Diseases. J Alzheimers Dis Parkinsonism. 2014;4:141.
- Gardener S et al. Dietary Patterns Associated with Alzheimer’s Disease and Related Chronic Disease Risk: A Review. J Alzheimers Dis Parkinsonism. 2013;S10:005.
- Arikawa M et al. Donepezil, Therapeutic Acetylcholinesterase Inhibitor, Prevents the Progression of Ventricular Dysfunction by Promoting Myocardial Glucose Utilization in Rat Model of Chronic Heart Failure Following Myocardial Infarction. Cardiol Pharmacol. 2014;3:121.
- Jin H et al. Acetylcholinesterase and Butyrylcholinesterase Inhibitory Properties of Functionalized Tetrahydroacridines and Related Analogs. Med chem. 2014;4:688-696.
- Saldanha C and Silva-Herdade A. The Ubiquity Nature of Acetylcholine. Clin Exp Pharmacol. 2014;4:159.
- Yellamma K. Silk Protein, Sericin as a Cognitive Enhancer in Alzheimer’s Disease. J Alzheimers Dis Parkinsonism. 2014;4:163.
- Kim H et al. Differences in C-reactive Protein Level in Patients with Alzheimer’s Disease and Mild Cognitive Impairment. J Psychiatry. 2015;18:194.
- Eze CO et al. The Prevalence of Cognitive Impairment amongst Type 2 Diabetes Mellitus Patients at Abakaliki South-East Nigeria. J Metabolic Synd. 2015;4:171.
- Mamiya T et al. Pregerminated Brown Rice Enhanced NMDA Receptor/CaMKIIa Signaling in the Frontal Cortex of Mice. J Rice Res. 2014;2:123.
- Silva-Gómez AB et al. Short- and Long-Term Treatments with Dexamethasone have Different Effects on Spatial Learning and Memory. Clin Exp Pharmacol. 2014;4:161.
- Stella F. Neuropsychiatric Symptoms in Alzheimer’s Disease Patients: Improving the Diagnosis. J Alzheimers Dis Parkinsonism. 2014;4:1000146.
- Ganesh PS et al. Voltammetric Resolution of Dopamine in Presence of Ascorbic Acid and Uric Acid at Poly (Brilliant Blue) Modified Carbon Paste Electrode. J Anal Bioanal Tech. 2014;5:229.
- Ikemoto K et al. Prenatal Maternal Stress Due to Repeated Exposure to A Cold Environment Affects Development of Catecholamine Neurons in Rat Offspring: An Imunohistochemical Study. J Neurol Neurophysiol. 2015;6:271.
- Kenneth Blum et al. Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)? J Addict Res Ther. 2014;5:185.
- Blum K et al. Can Genetic Testing Coupled with Enhanced Dopaminergic Activation Reduce Recidivism Rates in the Workers Compensation Legacy Cases?. J Alcohol Drug Depend. 2014;2:161.
- Field T. Smell and Taste Dysfunction as Early Markers for Neurodegenerative and Neuropsychiatric Diseases. J Alzheimers Dis Parkinsonism. 2015;5:186.
- Sneider JT et al. Differential Effects of Binge Drinking on Learning and Memory in Emerging Adults. J Addict Res Ther. 2013;S7:006.
- Chen D et al. A New Vanadium Complex Improves the Spatial Learning and Memory by Activation of Caveolin- MAPK-CREB Pathway in Diabetic Mice. J Diabetes Metab. 2011;2:114.
- Saint-Pol J et al. The LXR/RXR Approaches in Alzheimer’s Disease: Is the Blood-Brain Barrier the Forgotten Partner? J Alzheimers Dis Parkinsonism. 2013;3:e131.
- Yaghmoor F et al. The Role of TREM2 in Alzheimer’s Disease and Other Neurological Disorders. J Alzheimers Dis Parkinsonism. 2014;4:160.
- Zhang C. The WD40 Repeat Protein Mutations: Genetics,Molecular Mechanisms and Therapeutic Implications. J Genet Syndr Gene Ther. 2014;5:252.
- Downer EJ. Toll-Like Receptor Signaling in Alzheimer’s Disease Progression. J Alzheimers Dis Parkinsonism. 2013;S10:006.
- Yiannakopoulou ECh. Pharmacovigilance and NSAIDs J Pharmacovigilance. 2014;2:e116.
- Nalamachu S et al. Acute Pain Management in the Emergency Department: Emphasis on NSAIDs. Emergency Med. 2013;4:171.
- Ekinci F et al. A Rare Case of Rhabdomyolysis Probably Due to Donepezil. J Clin Case Rep. 2014;4:465.
- Miyaoka T et al. Effect of Donepezil on Sleep and Activity in Alzheimerâ€™s Disease: Actigraphic and Polysomnographic Assessment. J Alzheimers Dis Parkinsonism. 2014;4:157.
- Pourcher E et al. Donepezil and Selegiline to Improve Balance Control in Early Progressive Supranuclear Palsy. J Neurol Disord. 2014;2:153.
- Meier-Davis SR et al. Comparison of Metabolism of Donepezil in Rat, Mini-Pig and Human, Following Oral and Transdermal Administration, and in an in vitro Model of Human Epidermis. J Drug Metab Toxicol. 2012;3:129.
- Meier-Davis SR et al. Absorption, Distribution and Excretion Pattern of Oral and Transdermal Donepezil Hydrochloride after Single and Repeated Administration to the Rat. J Drug Metab Toxicol. 2012;3:123.
- Miyaoka T eta l. Effect of Donepezil on Sleep and Activity in Alzheimer’s Disease: Actigraphic and Polysomnographic Assessment. J Alzheimers Dis Parkinsonism. 2014;4:157.
- Olalekan O and Sanya OJ. NMDA R/VDR in Fish Melanocytes; Receptor Targeted Therapeutic Model and Mechanism in Parkinson's disease. J Biomol Res Ther. 2014;3:114.
- Bunik VI. Benefits of Thiamin (Vitamin B1) Administration in Neurodegenerative Diseases May Be Due to Both the Coenzyme and Non-coenzyme Roles of Thiamin. J Alzheimers Dis Parkinsonism. 2014;4:173.
- Luong Kvq and Nguyen LTH. Environmental Factors in Alzheimer’s and Parkinson’s Diseases. J Alzheimers Dis Parkinsonism. 2013;3:119.
- Naidoo DP. Neurocirculatory Manifestations of Thiamine Deficiency. Emerg Med (Los Angel). 2015;5:236.
- Spector R. Vitamin Transport Diseases of Brain: Focus on Folates, Thiamine and Riboflavin. Brain Disord Ther. 2014;3:120.
- Moss CJ and Mathews ST. Thiamin Status and Supplementation in the Management of Diabetes Mellitus and its Vascular Comorbidities. Vitam Miner. 2013;2:111.
- Stephenson D et al. Alzheimer’s and Parkinson’s Diseases Face Common Challenges in Therapeutic Development: Role of the Precompetitive Consortium, Coalition Against Major Diseases. J Alzheimers Dis Parkinsonism. 2015;5:183.
- Miller MD and Morycz RK. Preparing for the Rise in Alzheimers Disease Cases: A Proposal for Training Support Personnel. J Gerontol Geriatr Res. 2015;4:1000195.
- Basak UC et al. Assessment of Protective Antioxidant Mechanisms in some Ethno-Medicinally Important wild Edible Fruits of Odisha, India. Agrotechnol. 2013;2:116.
- Petkar Medha B et al. Purification and Characterization of Superoxide Dismutase Isolated From Sewage Isolated E. coli. J Microb Biochem Technol. 2013;5:102-106.
- Waghmare S et al. Immunoproteomics Approach for Development of Synthetic Peptide Vaccine from Thioredoxin Glutathione Reductase. Metabolomics. 2012;2:111.
- Mustafa HIS. Staphylococcus Aureus can Produce Catalase Enzyme when React with Human Wbcs as a Source of H2O2 Productions in Human Plasma or Serum in the Laboratory. J Med Microb Diagn. 2014;3:160.
- Younes AKH et al. Lack of Association between Catalase Gene Polymorphism and Susceptibility to Vitiligo in an Egyptian Population. Pigmentary Disorders. 2014;3:124.
- Sarmento-Silva AJ et al. Alpha-Tocopherol Counteracts Cognitive and Motor Deficits Induced by Repeated Treatment with Reserpine. Biochem Pharmacol (Los Angel). 2014;4:153.
- Nakase T et al. Edaravone, a Free Radical Scavenger, can Effect on the Inflammatory Biomarkers in Acute Ischemic Stroke Patients. J Neurol Disord. 2014;2:167.
- Kikuchi K et al. Beneficial Effects of the Free Radical Scavenger Edaravone (Radicut) in Neurologic Diseases. J Neurol Neurophysiol. 2011;S1.
- Jiao SS et al. Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits. Proceedings of the National Academy of Sciences. 2015;112.
- Kaufman AC et al. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Annals of Neurology. 2015;394.
- Chen A, Ou Y (2012) Glaucoma and Alzheimer Disease: Age-Related Neurodegenerative Diseases with Shared Mechanisms? J Clinic Experiment Ophthalmol S4:004.
- Donmez G. Aging and Neurodegeneration. J Mol Genet Med. 2015;7:071.
- Rajasekar N et al. Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice. European Journal of Pharmacology. 2013;715:381-394.
- Jana K et al. Caspases: A Potential Therapeutic Targets in the Treatment of Alzheimerâ€™s Disease. Transl Med. 2013;S2:006.
- Restini CBA et al. Integrative Approach of Venous Return And Cardiac Output in the Context of Skeletal Muscle Atrophy . J Clin Exp Cardiolog. 2014;5:355.
- McGrath RT et al. Central Functions of Glucagon-like Peptide-1: Roles in Energy Regulation and Neuroprotection. J Steroids Horm Sci. 20156:152.