Therapeutic potential of stem cells and acitretin on inflammatory signaling pathway-associated genes regulated by miRNAs 146a and 155 in AD-like rats.

Alzheimer's disease (AD) is one of the most common causes of dementia. Several drugs are used to improve the symptoms, but do not stop AD progression. There are more promising treatments that may have a significant role in AD diagnosis and treatment such as miRNAs and stem cells. The present study aims to develop a new approach for AD treatment by mesenchymal stem cells (MSCs) and/or acitretin with special reference to inflammatory signaling pathway as NF-kB and its regulator miRNAs in AD-like rat model. Fourty-five male albino rats were allotted for the present study. The experimental periods were divided into induction, withdrawal, and therapeutic phases. Expression levels of miR-146a, miR-155, necrotic, growth and inflammatory genes were assessed using RT-qPCR. Histopathological examination of brain tissues was performed in different rat groups. The normal physiological, molecular, and histopathological levels were restored after treatment with MSCs and/or acitretin. The present study demonstrates that the miR-146a and miR-155 might be used as promising biomarkers for AD. MSCs and/or acitretin proved their therapeutic potential in restoring the expression levels of targeted miRNAs and their related genes concerning NF-kB signaling pathway.

miRNAs and Stem Cells as Promising Diagnostic and Therapeutic Targets for Alzheimer's Disease.

Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-ß peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-ß protein precursor, stimulating the non-amyloidogenic pathway for amyloid-ß protein precursor processing resulting in amyloid-ß reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.