Alzheimer's disease (AD) is a neurodegenerative disorder known to be the leading cause of dementia worldwide. Many microRNAs (miRNAs) were found deregulated in the brain or blood of AD patients, suggesting a possible key role in different stages of neurodegeneration. In particular, mitogen-activated protein kinases (MAPK) signaling can be impaired by miRNA dysregulation during AD. Indeed, the aberrant MAPK pathway may facilitate the development of amyloid-beta (Aβ) and Tau pathology, oxidative stress, neuroinflammation, and brain cell death. The aim of this review was to describe the molecular interactions between miRNAs and MAPKs during AD pathogenesis by selecting evidence from experimental AD models. Publications ranging from 2010 to 2023 were considered, based on PubMed and Web of Science databases. According to obtained data, several miRNA deregulations may regulate MAPK signaling in different stages of AD and conversely. Moreover, overexpressing or silencing miRNAs involved in MAPK regulation was seen to improve cognitive deficits in AD animal models. In particular, miR-132 is of particular interest due to its neuroprotective functions by inhibiting Aβ and Tau depositions, as well as oxidative stress, through ERK/MAPK1 signaling modulation. However, further investigations are required to confirm and implement these promising results.
Keywords: Alzheimer’s disease; MAPK; microRNAs; neurodegeneration.