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ALZHEIMERS DISEASETINNA DEVI A/P ARMASAMY @ ARUMUGAM 012014030400SHANTA MARIA A/P JOTHEE 012014030746MAGESWARI A/P SUNDRARAJA 012013111216

Decline in memory or other thinking skills that affects a person ability to perform daily activities.Damage to nerve cell in the brain(neurons)Neurons can no long function and may dieLead to changes in ones memory, behavior and ability to think clearlyINTRODUCTION DementiaAlzheimers DiseaseVascular DementiaDementia with Lewy Bodies (DLB)Frontotemporal lobar degeneration (FTLD)Mixed DementiaParkinsons Disease DementiaCreutzfeldt-Jakob diseaseNormal pressure hydrocephalusTYPES OF DEMENTIAMost common neurodegenerative diseasePrevalence is increasing with the longer life span of the human population60-80% of dementia cases have ADAccumulation of the protein fragment beta-amyloid(plaques) outside neurons in the brain and twisted strands of the protein tau(tangles) inside neuronsCause damage and death to neuron

ALZHEIMERS DISEASE (AD)

Genetic MutationsAgeFamily historyApolipoprotein E (APOE) 4 GeneMild Cognitive Impairment(MCI)Cardiovascular Disease Risk FactorsSocial and Cognitive EngagementEducationTraumatic Brain Injury

ETIOLOGY

AD interferes with the proper functioning of neurons and synapsesAccumulation of protein beta-amyloid outside neurons (plaques) & abnormal form of protein tau inside neurons (tau tangles)Plaques - It interferes the neuron-neuron communication at synapses causing cell deathTangles block the transport of nutrients and other essential molecules causing cell deathHence patients with AD will show brain shrinkage from cell loss and widespread of debris from dead and dying neurons

PATHOGENESISMemory lossChallenges in planning or solving problemsDifficulty in completing familiar taskConfusion with time or placeTrouble understanding visual imagesNew problems with speaking & writingMisplacing things & losing the ability to retrace stepsPoor judgmentWithdrawal from workChanges in mood & personalitySYMPTOMSObtains medical & family historyLook into psychiatric history & history of cognitive & behavioral changesConducts cognitive tests & physical & neurological examinations (MRI)Biomarkers testDIAGNOSISAD may begin 20 or more years before symptoms appearSymptoms more worsen till bed riddenSecondary disease infection may lead to deathPROGNOSISPharmacologic treatmentUsing medication, increase neurotransmitters in brainNon-pharmacologic treatmentPhysical therapyTREATMENTPre-clinical ADEducationIndulging in activities that maintain healthy brainContinuous challenge to brain

PREVENTIONAyurveda is being seen as a rich resource for new drug development by modern day researchersCanscora decussata - xanthoneAyurvedic drug for its action in CNSFor boosting memory and improving intellectHas therapeutic effects on CNS disorders like epilepsy, insanity & memory enhancementNardostachys jatamansi - nardal & Mucuna pruriens - ergotamineBIOINFORMATIS IN AD STUDIESAyur-informatics: Establishing an in-silico-ayurvedic medication forAlzheimers disease12

Nardostachys jatamansi

Mucuna pruriens

Canscora decussataModeller9v7Swiss-Pdb Viewer v4.01ACD/ Chem SketchRAMPAGEArgus LabHex 5.1PATCHDOCKMETHODOLOGYAD causing proteins- APP, APOE, Presenilin 1 and Presenilin 2 were taken from NCBI entrez system

Homology modeling was carried out using Modeller 9v7, for predicting 3 D structuresFor the above mentioned proteins, homology modeling was done using Modeller 9v7Templates used for it were homologous protein structures from RCBS PDB database5 models of each of the above proteins were generated & analyzed by Rampage Ramchandran plot server and the best model of each was selectedChemical structures of active component of each species were drawn and combined using ACD Chem Sketch software.This combination structure was saved as *.mol file and was later converted to *.pdb file using Argus lab software

3D structure of APP obtained by homology modeling was analyzed by Rampage Ramchandran plot serverNumber of residues in favored region(~98.0% expected): 381 (92.9%)Number of residues in allowed region(~2.0% expected): 22 (5.4%)Number of residues in outlier region : 7(1.7%)

RESULTS

Docking is successful and proven effective in treating ADThis in-silico-herbal work makes use of ayurvedic herbs in Computer Aided Drug DesigningHomology Modelling is used to model the 3D structure of the proteinssince the work is done in in-silico platform, the combination needs to go to clinical testing to establish its efficacySUMMARYHence, bioinformatics plays an important role in drug designing for ADIt saves cost and timeContinuous research should be done to find the cure for ADCONCLUSIONMohini Gore*, Preenon Bagchi, Desai N.S. and Ajit Kar in Ayur-informatics: Establishing an in-silico-ayurvedic medication for Alzheimers diseaseJoseph Gaugler, Ph.D., Bryan James, Ph.D., Tricia Johnson, Ph.D., Ken Scholz, Ph.D., and Jennifer Weuve, M.P.H., Sc.D., in the preparation of 2014 Alzheimers Disease Facts and Figures.

REFERENCES