Regulatory Relationship of microRNAs in Alzheimer and Huntington Diseases: A Cladistics Approach Prachi Srivastava AMITY Institute of Biotechnology AMITY University Uttar Pradesh Lucknow Lucknow, UP, India

AMITY INSTITUTE OF BIOTECHNOLOGY INTRODUCTION 2

AMITY INSTITUTE OF BIOTECHNOLOGY RNA interference (RNAi) RNA interference (RNAi) is a highly evolutionally conserved process of post-transcriptional gene silencing (PTGS) double stranded RNA (dsRNA), when introduced into a cell, causes sequence-specific degradation of homogolous mRNA sequences. It was first discovered in 1998 by Andrew Fire and Craig Mello in the nematode worm Caenorhabditis elegans and later found in a wide variety of organisms, including mammals

AMITY INSTITUTE OF BIOTECHNOLOGY T IMELINE cosuppression of purple color in plants dsRNA injection in worms short RNAs identified in plants RNAi shown in vitro RISC activity partially purified siRNAs identifiedDicer identified RNAi used against HIV genome-wide RNAi screens begin

AMITY INSTITUTE OF BIOTECHNOLOGY RNA Interference Phenomena first observed in petunia Attempted to overexpress chalone synthase (anthrocyanin pigment gene) in petunia. (trying to darken flower color) Caused the loss of pigment. Called co-suppression because suppressed expression of both endogenous gene and transgene

AMITY INSTITUTE OF BIOTECHNOLOGY RNA Interference Approaches Four types of responses induced by dsRNA 6

AMITY INSTITUTE OF BIOTECHNOLOGY The Mechanism of RNAi 7

AMITY INSTITUTE OF BIOTECHNOLOGY MicroRNA(miRNA) 8

AMITY INSTITUTE OF BIOTECHNOLOGY miRNA vs. siRNA 9

AMITY INSTITUTE OF BIOTECHNOLOGY Integration of RNAi in Drug Discovery 10

AMITY INSTITUTE OF BIOTECHNOLOGY RNAi based therapeutics 11

AMITY INSTITUTE OF BIOTECHNOLOGY RNA-interference-based therapies 12

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AMITY INSTITUTE OF BIOTECHNOLOGY METHODOLOGY 14

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AMITY INSTITUTE OF BIOTECHNOLOGY RESULT AND CONCLUSION 20

AMITY INSTITUTE OF BIOTECHNOLOGY Alzheimer and Huntington 21

AMITY INSTITUTE OF BIOTECHNOLOGY Alzheimer and Huntington S no.miRNAGene familyRegulation patternBootstrap score 1.Mir-22(H)MIPF Down Regulated10 Mir-22(A) 2.Mir-330(H)MIPF Up Regulated5.17 Mir-34a(A)MIPF Down Regulated 3.Mir-132(H)MIPF Down Regulated5.00 Mir-298(A)MIPF Down Regulated 4.Mir-128-1(H)MIPF Down Regulated10 Mir-128-1(A)Up Regulated 5.Mir-29a(H)MIPF Up Regulated10 Mir-29a(A)Down Regulated 22

AMITY INSTITUTE OF BIOTECHNOLOGY Alzheimer and Parkinson 23

AMITY INSTITUTE OF BIOTECHNOLOGY Alzheimer and Parkinson S no.miRNAGene family Regulation pattern Bootstrap score 1.Mir-26a-1(P)MIPF Down regulated10 Mir-26b(A) 2.Mir-184(P)MIPF N/A- Mir-320(A)MIPF Up regulated 24

AMITY INSTITUTE OF BIOTECHNOLOGY Parkinson and Huntington 25

AMITY INSTITUTE OF BIOTECHNOLOGY Parkinson and Huntington S no.miRNAGene familyRegulation patternBootstrap score 1.Mir-184(P)MIPF Down regulated10 Mir-132(H)MIPF Mir-133(P)MIPF Down regulated6 Mir-128-1(H)MIPF

AMITY INSTITUTE OF BIOTECHNOLOGY CONCLUSION Phylogenetic analysis of miRNA of Alzheimer and Huntington diseases gives insight into evolutionary relationship and reveals regulation of Mir-22, Mir 29a, and mir in both diseases. Mir-22 shows down-regulation in Parkinson disease and Alzheimer disease while mir and mir-29a shows the difference in their regulation pattern In Alzheimer disease mir is up regulated while in Huntington disease it is down regulated. Mir-29a is up regulated in Huntington disease while in Alzheimer disease, it is down regulated. These findings illustrates the importance of miRNA research in Neurodegenerative diseases with reference to novel targets identification which can give a better lead in concern to protective or prophylective approaches. 27

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