microRNA-34a (miRNA-34a) Mediated Down-Regulation of the Post-synaptic Cytoskeletal Element SHANK3 in Sporadic Alzheimer's Disease (AD)

Frontiers in Neurology
Yuhai ZhaoWalter J Lukiw

Abstract

Integrating a combination of bioinformatics, microRNA microfluidic arrays, ELISA analysis, LED Northern, and transfection-luciferase reporter assay data using human neuronal-glial (HNG) cells in primary culture we have discovered a set of up-regulated microRNAs (miRNAs) linked to a small family of down-regulated messenger RNAs (mRNAs) within the superior temporal lobe neocortex (Brodmann A22) of sporadic Alzheimer's disease (AD) brain. At the level of mRNA abundance, the expression of a significant number of human brain genes found to be down-regulated in sporadic AD neocortex appears to be due to the increased abundance of a several brain-abundant inducible miRNAs. These up-regulated miRNAs-including, prominently, miRNA-34a-have complimentary RNA sequences in the 3' untranslated-region (3'-UTR) of their target-mRNAs that results in the pathological down-regulation in the expression of important brain genes. An up-regulated microRNA-34a, already implicated in age-related inflammatory-neurodegeneration-appears to down-regulate key mRNA targets involved in synaptogenesis and synaptic-structure, distinguishing neuronal deficits associated with AD neuropathology. One significantly down-regulated post-synaptic element in AD is the p...Continue Reading

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Citations

Nov 23, 2019·Molecular Neurobiology·Birgitte BerentsenClive R Bramham
Jun 18, 2020·Brain Sciences·Gloria Ortiz-GuerreroMauricio O Nava-Mesa
May 29, 2020·Genes & Genomics·Minseok Song
Jul 18, 2020·International Journal of Molecular Sciences·Alex Cleber Improta-CariaBruno Solano de Freitas Souza
Jun 12, 2019·Molecular Neurobiology·Vivian R JaberWalter J Lukiw
Aug 10, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Maryam BazrgarAbolhassan Ahmadiani

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Datasets Mentioned

BETA
AB569469.1

Methods Mentioned

BETA
transgenic
ELISA

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