Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases

Abstract

The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs—i.e., Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)—as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.

Bibliometric analysis of research on Alzheimer’s disease and non-coding RNAs: Opportunities and challenges

“…In recent years, most research on the role of ncRNAs from different sources in AD have been published. In fact, ncRNAs are not only found in nerve cells but can also be detected in blood and cerebrospinal fluid, suggesting that ncRNAs from different tissue may have different clinical significance ( Nikolac Perkovic et al, 2021 ; Doroszkiewicz et al, 2022 ). In fact, the expression level of ncRNAs in different tissues may also be different, which also makes it difficult to explore biomarkers for AD.…”

Recent Advances in the Roles of MicroRNA and MicroRNA-Based Diagnosis in Neurodegenerative Diseases

“…A group of miRNAs have been reported as prognostic biomarkers for ALS [ 201 ]. After an investigation of 252 ALS patients, it was concluded that circulating miR-181 was a prognostic biomarker for the disease [ 202 ].…”

The Potential Connection between Molecular Changes and Biomarkers Related to ALS and the Development and Regeneration of CNS

“…Moreover, in patients with ALS, some studies have shown the changing patterns of methylation in ALS-related genes [ 57 , 58 , 59 ] and connected the engagement of the epigenetic mechanisms in motor neuron apoptotic cell death through DNA methylation, which is essential during the development of the nervous system and could be relevant to human ALS pathobiology [ 60 ]. The results of several studies suggest that epigenetic changes (through methylation and noncoding RNAs) may represent new biomarkers and contribute to the development of new ALS therapies (reviewed in [ 61 , 62 , 63 ]). Moreover, we propose that the overlap and correlation in the expression of the selected biomarkers during early CNS development and in ALS patients could narrow down the number of potential candidates, as well as open new insights into disease pathogenesis.…”