Table 3.
Description of cross-link between NF-KB and altered miRNAs in various pathological conditions.
| Disease | Mutated Gene Involved | Atypical Expressed miRNA | NF-KB Role & Pathological Implications | Refs. |
|---|---|---|---|---|
| Alzheimer disease | BACE1, IRAKI, ERK1, PTBP1, FMR1. | mRNA 3’UTR for (miR-29a/b-1, miR-15a, miR-146 a miR-9, miR-20a, miR-1-5p, miR-106p miR-19b, miR-107). Expansion of CGG in 5’UTR for miR-125 b; miR- 132. |
Increased production of Amyloid beta in anterior temporal cortex, Increased inflammation, Overactivation of tau, Abnormal APP mRNA alternating splicing, Altered synaptic plasticity. |
[227-229] |
| Parkinson’s disease | RRK2, DJ-1, PTEN-induced kinase 1 (PINK1), Parkin, α-synuclein, leucine-rich repeat kinase 2 (LRRK2), Pitx3 |
Down regulation of precrsor-let7a-1, pre-miR7-2, pre-miR-99a, pre-miR7-130, pre-miR-133b, pre-miR-136, pre-miR-224, and pre-miR-143., pre-miR-133b, pre-miR-218-2, pre-miR-15b, pre-miR pre-miR pre-miR-101-1, pre-miR-107, pre-miR-335, pre-miR -345; miR-7 & miR-153; miR-34b and miR-34c. miR-146a, miR-124. |
Loss of dopaminergic neurons in the mid-brain, Pitx3 deficiency results in selective loss of nigrostriatal DA, Increased α-Synuclein undergoes oxidative stress causing dopaminergic degeneration. LRRK2 inhibits let-7 and miR-184 and causes cell death. Depletion of miR-34b and miR-34c causes reduction of Parkin and DJ-1 necessary for mitochondrial homeostasis and cellular redox balance. |
[145, 154-156] |
| Amyotrophic Lateral Sclerosis (ALS) | C90rf72, SOD1, TARDBP, FUS. |
Expansion of a GGGGCC hexanucleotide more than 30 repeats upstream of the C9orf72; GLT1mRNA. |
frontotemporal lobar degeneration by aggregation of TD43 protein and causing endoplasmic stress mediating neuronal death. Mutated SOD1 targets Glial glutamate transporter GLT1 by decreasing its expression and further impairment of motor dysfunction. Impairment of proteasome-mediated protein degradation. |
[230-233] |
| Prion disease | PrP gene. | PrP mRNA, Increased miR-16, miR-14a, expression causes inflammation signalling. |
Missfolding of the prion protein causes endoplasmic stress. |
[234, 235] |
| Depression | BDNF, GPM6A, GPM6B. | BDNF-mRNA, Downregulated GPM6A & GPM6B. |
Decreased neuronal plasticity. | [236, 237] |
| Huntington’s disease (HD) | HTT gene. | Mutated CAG trinucleotide in the exon 1 of htt gene. | Abnormal longer polyglutamine (poly Q) stretch (wild- type htt protein) causing neuronal death. | [120, 121] |
| Spinocerebellar ataxia (SCA) | ATXN1. | Repetition of CAG trinucleotide expanding poly Q in ATXN1 protein. miR-19, miR-101, miR-150, miR-181 and miR-130 |
Downregulation of miR-19, miR 181 increases the expression of NF-KB causing Cerebellum purkinje neurons atrophy and glutaminergic synaptic loss. | [130-133] |
| Cerebral ischemia | BCL-2, BCL-w, SOD2. | miR-320, miR-145, miR -210, miR- 497, miR-181, miR-183, miR-215 and miR-22. |
Downregulation of miR-183, miR-215, miR-22 and upregulation of miR-181 increase the inflammation-causing excitotoxicity. | [160-162] |
| Traumatic brain injury | IL-1, TNF- alpha. | miR-144, miR- 153, miR-340-5p, miR-155, miR-223, miR-124-3p. | Up-regulation of miR-155, miR-223 promotes the inflammation and down-regulation of miR-124-3p promotes the apoptotic neuronal death. | [170-172] |
| Depression | BDNF, NPTX2, TNF-alpha, IL-1 β, IL-6, | let-7e, let-175p, miR -301b, miR -221-3p, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, miR-175p. | up regulating of miR-221-3p, let-7e, miR-223, miR-145, miR-155 and miR-146a increases the inflammation which causes disruption of neurogenesis in depression. | [175-179] |
| Epilepsy | TNF-alpha, IL-1 β, IL-6, HMGB1, | Upregulation of miR-210, miR-30, miR-27a, miR-183, miR- 134, miR-135a, miR-125b, miR-148a, miR- 146a, miR-124 whereas, the downregulation of miR-128, miR-199a, miR-21a, miR-22. | Dysregulation of miR-181a, miR-129-5p, miR-124, miR- 146a, miR-155 increases the neuroinflammation in epilepsy. | [188-197] |