Small Extracellular Vesicles’ miRNAs: Biomarkers and Therapeutics for Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are critical in the healthcare system as patients suffer from progressive diseases despite currently available drug management. Indeed, the growing ageing population will burden the country’s healthcare system and the caretakers. Thus, there is a need for new management that could stop or reverse the progression of neurodegenerative diseases. Stem cells possess a remarkable regenerative potential that has long been investigated to resolve these issues. Some breakthroughs have been achieved thus far to replace the damaged brain cells; however, the procedure’s invasiveness has prompted scientists to investigate using stem-cell small extracellular vesicles (sEVs) as a non-invasive cell-free therapy to address the limitations of cell therapy. With the advancement of technology to understand the molecular changes of neurodegenerative diseases, efforts have been made to enrich stem cells’ sEVs with miRNAs to increase the therapeutic efficacy of the sEVs. In this article, the pathophysiology of various neurodegenerative diseases is highlighted. The role of miRNAs from sEVs as biomarkers and treatments is also discussed. Lastly, the applications and delivery of stem cells and their miRNA-enriched sEVs for treating neurodegenerative diseases are emphasised and reviewed.

Luteolin/ZnO nanoparticles attenuate neuroinflammation associated with diabetes via regulating MicroRNA‐124 by targeting C/EBPA

“…54 MiR-124 plays an important role in the promotion of diverse anti-inflammatory effects by blocking the production of proinflammatory cytokines such as IL6 and TNF. 36 The current study found that STZ-induced diabetes caused depilation of miR-124 in brain tissues, which was associated with activation of TNF-α, IL-1β, IL-4, IL-10, NF-Kb p65, and C/EBP-levels. The C/EBP, a transcription factor involved in myeloid cell development, was thought to be a potential target, and with one intact miR-124 binding site within its 3 0 untranslated sequence downregulating the C/EBP-α-PU1 axis to reduce autoimmune encephalomyelitis.…”

“…Evidence indicates that miR-124 is a crucial modulator of peripheral and CNS inflammatory processes by limiting microglia and macrophage activation and decreasing pro-inflammatory cytokine production. 36 However, the fundamental mechanism remains unknown. Notably, we would show that miR-124 has a possible neuroprotective impact in the neuroinflammation associated with diabetes rat model.…”

“…MiR‐124 has been shown in studies to reduce neuron loss in a variety of neurodegenerative illnesses. Evidence indicates that miR‐124 is a crucial modulator of peripheral and CNS inflammatory processes by limiting microglia and macrophage activation and decreasing pro‐inflammatory cytokine production 36 . However, the fundamental mechanism remains unknown.…”

“…In particular, miR 124 is one of the most prevalent miRNAs in the brain, which regulates neuronal differentiation and is reduced in ischemic stroke 54 . MiR‐124 plays an important role in the promotion of diverse anti‐inflammatory effects by blocking the production of proinflammatory cytokines such as IL6 and TNF 36 . The current study found that STZ‐induced diabetes caused depilation of miR‐124 in brain tissues, which was associated with activation of TNF‐α, IL‐1β, IL‐4, IL‐10, NF‐Kb p65, and C/EBP‐ levels.…”