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I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression MicroRNAs that assist in early diagnosis of Alzheimer's and depression
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microRNA in Alzheimer’s disease and Depression
I International Symposium: Neurobiology and Biomarkers of Brain Aging
Ana Paula Mendes SilvaPhD Student
Federal University of Minas Gerais/UFMG
miRNA
Biomarkers
CharacteristicsAdvantages and
limitations
Major depressive disorder
Alzheimer’s disease
Gene therapy
http://www.mdpi.com/2075-4418/3/1/84/htm
• Non-coding RNA
CharacteristicsCharacteristics
http://mcb.berkeley.edu/labs/he/Research.htm
miRNA
• microRNAs mediate translational repression or mRNA degradation
Post-transcriptional regulators of gene expression
18 to 22-nucleotides-long
• Horizontal transfer of miRNAs by secreted extracellular vesicles -> intercellular communication
CharacteristicsCharacteristics
http://circres.ahajournals.org/content/110/3/483.abstract
• A single miRNAs can target multiple mRNAs
CharacteristicsCharacteristics
hsa-miR-664
SLC10A2
ARID1A
PKN2
COPG
ZNF423 GPHN
IRF2
STRAP
ARID1B
CPEB4
KCMF1
ADCYAP1MDGA2
KLF12
AHCTF1PAHCTF1
FRMPD4
RSBN1
FAM7A3 BHLHB9
FAM7A1
ZMYND11
CT47A9
SMYD1
TTC33
RBM26
• Multiple miRNAs can target a single mRNA
CharacteristicsCharacteristics
BDNF
hsa-miR-1
hsa-miR-206
hsa-miR-613
hsa-miR-374b hsa-miR-495
hsa-miR-374a
hsa-miR-10a
hsa-miR-195
hsa-miR-216b
hsa-miR-122
hsa-miR-30a
hsa-miR-30e
BiomarkerBiomarker
• A biomarker is an indicator of physiological, biochemical, or anatomic parameter
Biological Biological ProcessesProcesses
Pathological Pathological ProcessesProcesses
Therapeutic Therapeutic InterventionIntervention
BiomarkerBiomarker
• miRNAs can be detected in serum, plasma, urine, and other biological fluids
Body fluidsBody fluids
http://www.mirnabodymap.org/
AdvantagesAdvantages
• Horizontal transfer
• Mature miRNAs are small
• Stable molecules
• Resistant to RNA degradation
• Highly conserved among species
• Differentiate pathological phenotypes
• Provide global disease profiling
• Customized treatment:
– Rational drug selection
– Monitoring response to therapy
• Alows risk stratification
AdvantagesAdvantages
• Noninvasive biomarkers
• Positive impact in patient comfort
• Can lead to early diagnosis
• Might enable patients to get on treatments earlier, preventing the devastanting effects of the disease
AdvantagesAdvantages
LimitationsLimitations
• It’s difficult to measure each miRNA contribuition to the disease
• The presence of miRNAs in collected fluids does not directly indicate the inhibition of the translation process
• Although a single miRNA can be related with multiple pathologies it does not necessarily mean that all the pathologies will develop
• Cost of miRNA sequencing
Meta-analysisMeta-analysisId
enti
ficat
ion Records identified through Web of
Science
Scre
enin
gIn
clud
edEl
igib
ility
Records identified through PubMed
Records after duplicates removed
Records screened
Records excluded, because they are reviews, book chapters,
meeting abstracts, descriptive articles and protocoll papers
Full-text articles accessed for eligibility
Full-text articles excluded, miRNAs specific cell, animal
models and the blood of patients under the use of any
medication
Studies included in the analysis
Records identified through SCOPUS
http://www.prisma-statement.org/
6 AD 3 D
416 AD 176 D
Alzheimer’s diseaseAlzheimer’s disease• The words used to identify the miRNAs related to
Alzheimer’s were: Alzheimer’s disease and miRNA.
• Identified 77 miRNAs differently expressed
miRNAs searchmiRNAs search
NetworkNetwork
447 genes
Major depressive disorderMajor depressive disorder
• The words used to identify the miRNAs related to depression were: (Major depressive disorder OR depressive disorder OR depression) and miRNA.
• Identified 32 miRNAs differently expressed
NetworkNetwork
210 genes
MiRNAs common to Alzheimer’s disease and MiRNAs common to Alzheimer’s disease and depressiondepression
hsa-miR-26b
hsa-miR-664
hsa-let-7d
hsa-let-7g
hsa-let-7fhsa-miR-191
hsa-miR-30d hsa-miR-361-5p
155 genes155 genes
5418
5467
5544
7467
6114
2015
8089
5616
NetworkNetwork
• Up-regulated – AntagomiRs are used to decrease the levels of
specific miRNA
• Down-regulated– Synthetic RNAs or siRNAs are used to increase the
levels
Gene therapyGene therapy
Gene therapyGene therapy
miRNAs Regulation FoldChange
hsa-miR-766-3p Down-regulated 9,54
hsa-miR-26b-5p Down-regulated 8,58
hsa-miR-340-5p Up-regulated 7,61
hsa-miR-6509-5p Up-regulated 7,43
cel-miR-39 Baseline (endogenous) _____________
Genome-wide sérum microRNA expression. Profiling identifies sérum biomarkers for Alzheimer’s disease. Tan, L.; Yu,J.T.; Tan, M.S.; Liu, Q.Y.; Wang, H.F.; Zhang, W.; Jiang, T. and Tan.L. Journal of Alzheimer’s disease 40 (2014) 1017-1027.
Thank You for your atention!Thank You for your atention!
e-mail: apmendes@ufmg.br
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