Extracellular RNAs as Biomarkers of Sporadic Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases

Abstract

Recent progress in the research for underlying mechanisms in neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) has led to the development of potentially effective treatment, and hence increased the need for useful biomarkers that may enable early diagnosis and therapeutic monitoring. The deposition of abnormal proteins is a pathological hallmark of neurodegenerative diseases, including β-amyloid in AD, α-synuclein in PD, and the transactive response DNA/RNA binding protein of 43kDa (TDP-43) in ALS. Furthermore, progression of the disease process accompanies the spreading of abnormal proteins. Extracellular proteins and RNAs, including mRNA, micro RNA, and circular RNA, which are present as a composite of exosomes or other forms, play a role in cell–cell communication, and the role of extracellular molecules in the cell-to-cell spreading of pathological processes in neurodegenerative diseases is now in the spotlight. Therefore, extracellular proteins and RNAs are considered potential biomarkers of neurodegenerative diseases, in particular ALS, in which RNA dysregulation has been shown to be involved in the pathogenesis. Here, we review extracellular proteins and RNAs that have been scrutinized as potential biomarkers of neurodegenerative diseases, and discuss the possibility of extracellular RNAs as diagnostic and therapeutic monitoring biomarkers of sporadic ALS.

The Role of the Microbiota–Gut–Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases

“…After sufficient time had passed, the results were then gathered and analyzed, and the authors found that 545 participants had passed away from ALS. The results of this study did not suggest there was any significant association between caffeine and ALS pathology to be protective or adverse [121].…”

Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

“…Furthermore, recent works have depicted their role as next-generation biomarkers based on their feasibility as therapeutic drug-delivery nanocarriers. In immunotherapy, they have generated much excitement as candidates for diagnostics and therapeutics in an array of diseases [24][25][26][27][28]. In this current study, we performed ultrastructural characterization of BDEV, their biogenesis, and identification of signatures using quantitative mass spectrometry-based proteomics from male and female Sprague Dawley rats following either long-term nicotine or saline self-administration.…”

An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease

“…Rapid diagnosis and intervention in the disease process could be beneficial in slowing neurodegenerative disease progression as well as facilitating the testing of new therapies. In ALS/MND, the average time from diagnosis to death is typically short (2–5 years) and it is not unusual for patients to wait a year before receiving a diagnosis [ 1 ]. Since disease progression correlates with motor neuron loss, early intervention could be critical for the development of new effective drug therapies.…”

“…To date, an ALS/MND diagnosis is based on clinical features with the elimination of alternative diagnoses and supporting data retrieved from electromyograms, nerve conduction studies, muscle biopsies, magnetic field imaging and biofluid analysis [ 3 , 4 ]. The search for ALS/MND biomarkers useful for diagnosis, prognosis and analysis of drug efficacy includes a variety of molecules found in biofluids and other techniques including: heavy and light chain neurofilaments, TAR DNA-binding protein 43 (TDP-43), a lipid peroxidation product (4-hydroxy-2,3-nonenal), a urinary neurotrophin receptor p75 extracellular domain, cystatin C, mRNA, miRNA, extracellular glutamate, markers of inflammation, microglial activation, electrical impedance myography, rate of disease progression, spinal cord imaging and others [ 1 , 5 – 17 ]. Thus far, none of these biomarkers have been sufficiently validated to be incorporated into the clinical standard of care [ 1 , 3 , 9 , 15 , 18 ].…”