LAUSR

Simple Summary Neurodegenerative diseases are complex neurological disorders with a high incidence worldwide in older people, increasing hospital visits and requiring expensive treatments. As a precursor phase of neurodegenerative diseases, cognitive impairment needs to be studied to understand the factors that influence its development and improve patients’ quality of life. The present review compiles possible factors and biomarkers for diagnosing mild cognitive impairment based on the most recent studies involving miRNAs. These molecules can direct the gene expression in multiple cells, affecting their behavior under certain conditions, such as stressing factors. This review encourages further research into biomarkers that identify cognitive impairment in cellular models such as astrocytes, which are brain cells capable of maintaining the optimal conditions for the central nervous system functioning. Abstract The importance of miRNAs in cellular processes and their dysregulation has taken significant importance in understanding different pathologies. Due to the constant increase in the prevalence of neurodegenerative diseases (ND) worldwide and their economic impact, mild cognitive impairment (MCI), considered a prodromal phase, is a logical starting point to study this public health problem. Multiple studies have established the importance of miRNAs in MCI, including astrocyte regulation during stressful conditions. Additionally, the protection mechanisms exerted by astrocytes against some damage in the central nervous system (CNS) lead to astrocytic reactivation, in which a differential expression of miRNAs has been shown. Nevertheless, excessive reactivation can cause neurodegeneration, and a clear pattern defining the equilibrium point between a neuroprotective or detrimental astrocytic phenotype is unknown. Therefore, the miRNA expression has gained significant attention to understand the maintenance of brain balance and improve the diagnosis and treatment at earlier stages in the ND. Here, we provide a comprehensive review of the emerging role of miRNAs in cellular processes that contribute to the loss of cognitive function, including lipotoxicity, which can induce chronic inflammation, also considering the fundamental role of astrocytes in brain homeostasis.