Neurodegenerative disorders are defined by neuronal loss and often associated with dementia. Understanding the multifactorial nature of cognitive decline is of particular interest. Cell loss is certainly a possibility but also an early imbalance in the complex gene networks involved in learning and memory. The small (~ 22 nt) non-coding microRNAs play a major role in gene expression regulation and have been linked to neuronal survival and cognition. Interestingly, changes in microRNA signatures are associated with neurodegenerative disorders. In this review, we explore the role of three microRNAs, namely miR-132, miR-124 and miR-34, which are dysregulated in major neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Interestingly, these microRNAs have been associated with both memory impairment and neuronal survival, providing a potential common molecular mechanism contributing to dementia.

Neuropathology Regulation Reported finding Techniques References
miR-132 AD Down Human hippocampus, prefrontal cortex and temporal gyrus of LOAD patients nCounter system, deep-sequencing and qRT-PCR Lau et al. (2013)
Down Human hippocampus, medial frontal gyrus and cerebellum of LOAD patients qRT-PCR Cogswell et al. (2008)
Down Human temporal cortex of load patients Multiplex qRT-PCR and qRT-PCR Wong et al. (2013)
Down Human temporal cortex of load patients Deep-sequencing and qRT-PCR Hebert et al. (2013)
Down human hippocampus, frontal lobe and temporal lobe of LOAD patients qRT-PCR Smith et al. (2015)
MCI Down Human temporal lobe of MCI patients qRT-PCR Smith et al. (2015)
Down Human frontal cortex of MCI patients Microarray (Exiqon miRCURY LNA) and qRT-PCR Weinberg et al. (2015)
Down Human serum of MCI patients qRT-PCR Xie et al. (2015)
PD Down Brainstem area of alpha-synuclein (A30P)-transgenic mouse LC Sciences microfluidic chip technology Gillardon et al. (2008)
Up Mesencephalic brain areas of Berlin-Druckrey IV rat affected Microarray (Chip ID miRRat 19.0 version) and qRT-PCR Lungu et al. (2013)
Up Human laser microdissected dopamine neurons of PD patients Human MicroRNA TaqMan® Arrays A 2.0 Briggs et al. (2015)
Down Human prefrontal cortex Brodmann Area 9 of HD patients small RNA-sequencing Hoss et al. (2016)
HD Down Striatum of YAC128 and R6/2 transgenic mouse Agilent Mouse miRNA Microarray and qRT-PCR Lee et al. (2011)
Down Human Brodmann area 4 of HD patients and cortex of R6/2 transgenic mouse qRT-PCR Johnson et al. (2008)
Down Human prefrontal cortex Brodmann Area 9 of HD patients Small RNA-sequencing Hoss et al. (2015)
Up Human Brodmann area 4 of HD patients qRT-PCR Packer et al. (2008)
miR-124 AD Down Human hippocampus of LOAD patients nCounter system Lau et al. (2013)
PD Down Substantia nigra of MPTP-induced PD mouse model qRT-PCR and in situ hybridization Kanagaraj et al. (2014)
Down Dopaminergic neurons within the substantia nigra of MPTP-induced PD mouse qRT-PCR and in situ hybridization Wang et al. (2015)
HD Down Cortex of R6/2 transgenic mouse model qRT-PCR Johnson et al. (2008)
Down Human Brodmann area 4 of HD patients qRT-PCR Packer et al. (2008)
Down Human frontal cortex and striatum of HD patients Deep sequencing and Agilent Human miRNA microarrays Marti et al. (2010)
miR-34a AD Up Human hippocampus, medial frontal gyrus and cerebellum of LOAD patients RT-qPCR Cogswell et al. (2008)
Up Cortex of APPswe/PSΔE9 transgenic mouse Dual-channel microarray μParaflo™ microfluidics chips Wang et al. (2009)
Up Human blood mononuclear cells of LOAD patients Human microRNA microarray (MMChip) Schipper et al. (2007)
miR-34b HD Up Mutant-HTT-transfected NT2 cell model and human plasma of HD patients miRCURY LNA miR v 11.0 arrays and miRNA RT-PCR Gaughwin et al. (2011)
Up Striatum of YAC128 and R6/2 transgenic mouse model Agilent Mouse miRNA Microarray Lee et al. (2011)
miR-34b/c PD Down Human amygdala, frontal cortex, substantia nigra and cerebellum of PD patients miRCURY™ array (Exiqon) and miRNA RT-PCR Minones-Moyano et al. (2011)
miR-34c AD Up Hippocampus of AD APPPS1–21 mouse and human hippocampus of LOAD patients Small RNA massive parallel sequencing and qRT-PCR Zovoilis et al. (2011)


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Reference

Hernandez-Rapp J, Rainone S, Hébert Sb. (2016) MicroRNAs underlying memory deficits in neurodegenerative disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry S0278-5846(16), 30057-4. [abstract]

 


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