Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by binding their 3′ untranslated region (3′UTR) region; these molecules play a fundamental role in several pathologies, including Alzheimer’s disease (AD). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a vesicular protein of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in neural plasticity and in the exocytosis of neurotransmitters, processes that are altered in AD. Recent results showed that a reduction of SNAP-25 is associated with dementia, and that the rs363050 SNAP-25 polymorphism correlates with cognitive decline and brain atrophy, as well as with the outcome of multistructured rehabilitation in AD patients. We verified the presence of possible correlations between the serum concentration of miRNAs that bind the SNAP-25 3′UTR region and AD. Six different microRNAs (miR-181a-5p, miR-361-3p, miR-23a-3p, miR-15b-3p, 130a-3p and miR-27b-3p) that bind the SNAP-25 3′UTR region were measured by qPCR in serum of AD patients (n = 22), mild cognitive impairment (MCI) subjects (n = 22) and age- and sex-matched controls (n = 22); analysis of results was done stratified for the rs363050 SNAP-25 genotype. Results showed that miR-27b-3p, miR-23a-3p and miR181a-5p serum concentration was significantly reduced in rs363050 SNAP-25 GG homozygous AD patients. Notably, concentration of these miRNAs was comparable in rs363050 AA homozygous AD patients, MCI and healthy controls (HCs). Data herein suggest that miRNAs that bind the SNAP-25 3′UTR region interact with SNAP-25 polymorphisms to influence the neural plasticity typical of AD brains, possibly as a consequence of modulatory activity on SNAP-25 mRNA and/or protein.
Highlights
Alzheimer’s disease (AD) is the most common age-related form of dementia (Alzheimer’s Association, 2014)
In the present pilot study, we verified whether serum concentration of the miRNAs that bind the 3 untranslated region (3 UTR) region of synaptosomal-associated protein 25 (SNAP-25) differs when AD, mild cognitive impairment (MCI) and healthy controls (HCs) individuals are compared and, if this was the case, whether the expression of these miRNAs is modulated by the SNAP-25 rs363050 polymorphism
The rs363050 single nucleotide polymorphism (SNP) of SNAP25 was shown to correlate with brain activity (Guerini et al, 2014) and the outcome of rehabilitation (Guerini et al, 2016) in AD patients
Summary
Alzheimer’s disease (AD) is the most common age-related form of dementia (Alzheimer’s Association, 2014). MiRNAs and SNAP-25 Genotype in AD complex involved in the exocytotic release of neurotransmitters during synaptic transmission (Antonucci et al, 2016), in neurological disorders, including AD (Noor and Zahid, 2017). MicroRNAs (miRNAs) are short non-coding RNAs (containing about 20–24 nucleotides) involved in mRNA silencing and post-transcriptional regulation of gene expression (Bartel, 2004) via their ability to bind the 3 untranslated region (3 UTR). MiRNAs are key players in the normal function of cells, and impairments in their modulation, regulation and/or expression are associated with pathologies including tumors (Castro et al, 2017; Drusco and Croce, 2017; Elghoroury et al, 2018; Koutsaki et al, 2017; Mansoori et al, 2017), stroke (Vijayan and Reddy, 2016) and type 2 diabetes mellitus (Liang et al, 2018). In the present pilot study, we verified whether serum concentration of the miRNAs that bind the 3 UTR region of SNAP-25 differs when AD, MCI and healthy controls (HCs) individuals are compared and, if this was the case, whether the expression of these miRNAs is modulated by the SNAP-25 rs363050 polymorphism
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