Extracellular Vesicles in Serum and Central Nervous System Tissues Contain microRNA Signatures in Sporadic Amyotrophic Lateral Sclerosis

Frontiers in Molecular Neuroscience, Год журнала: 2021, Номер 14

Опубликована: Окт. 29, 2021

Amyotrophic lateral sclerosis (ALS) is a terminalneurodegenerative disease. Clinical and molecular observations suggest that ALS pathology originates at single site spreads in an organized prion-like manner, possibly driven by extracellular vesicles. Extracellular vesicles (EVs) transfer cargo molecules associated with pathogenesis, such as misfolded aggregated proteins dysregulated microRNAs (miRNAs). However, it poorly understood whether altered levels of circulating or their components reflect pathological signatures the In this study, we used immuno-affinity-based microfluidic technology, electron microscopy, NanoString miRNA profiling to isolate characterize from frontal cortex, spinal cord, serum sporadic ( n = 15) healthy control 16) participants. We found larger cord versus controls smaller sized serum. there were no changes number between cases across any tissues. Characterization vesicle-derived compared identified significantly all tissues; miRNAs reduced cortex increased Two three tissues: miR-342-3p was ALS, miR-1254 ALS. Additional overlapping two tissues included miR-587, miR-298, miR-4443, miR-450a-2-3p. Predicted targets pathways common biological neurodegeneration, including axon guidance long-term potentiation. A predicted target one (N-deacetylase N-sulfotransferase 4; NDST4) likewise vitro model verifying potential relevance. Together, these findings demonstrate vesicle mirror those central nervous system disease state thereby offer insight into possible pathogenic factors diagnostic opportunities.

Язык: Английский

---

Extracellular Vesicles in Amyotrophic Lateral Sclerosis

Life, Год журнала: 2022, Номер 13(1), С. 121 - 121

Опубликована: Дек. 31, 2022

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease and the most common adult motor neuron disease. The pathogenesis complex with perturbation of multiple pathways proposed, including mitochondrial dysfunction, RNA processing, glutamate excitotoxicity, endoplasmic reticulum stress, protein homeostasis endosomal transport/extracellular vesicle (EV) secretion. EVs are nanoscopic membrane-bound particles that released from cells, involved in intercellular communication proteins, lipids genetic material, there increasing evidence their role ALS. After discussing biogenesis EVs, we review roles propagation pathological proteins ALS, such as TDP-43, SOD1 FUS, contribution to pathology. We also discuss ALS related genes which EV formation vesicular trafficking, before considering dysregulation found how these have been investigated potential biomarkers. Finally, highlight use therapeutic agents particular derived mesenchymal stem cells drug delivery vectors for treatment strategies.

Язык: Английский

---

Neurodegenerative Disorder and Fine Particulate Matter

Опубликована: Янв. 1, 2025

Abstract Extracellular vesicles (EVs), diverse membranous secreted by cells, include microvesicles, exosomes, and other cell-specific types. They efficiently deliver proteins nucleic acids to distal parts are implicated in the pathology of neurodegenerative disorders. Additionally, long-term exposure extracellular microparticles, notably particulate matter (PM) 2.5, is suspected induce neuroinflammation via oxidative stress mechanisms. Production macrovesicles relies on ARRDC1 ARF6/RhoA pathways, whereas exosome production involves both ESCRT-dependent ESCRT-independent pathways. In disorders, EVs play various roles: microglia-derived activate endothelial cells neurons stroke models, accelerate α-synuclein aggregation hinder autophagy Parkinson's disease, patient-derived muscle cell small (sEVs) worsen motor neuron death Amyotrophic lateral sclerosis (ALS), influence neuronal transmission through hippocampus, leading synaptic spine reduction Alzheimer's disease. However, precise mechanisms underlying involvement disease onset remain largely unknown, emphasizing need for further investigations.

Язык: Английский

---

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis

Nutrients, Год журнала: 2021, Номер 13(11), С. 3804 - 3804

Опубликована: Окт. 26, 2021

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the degeneration of motor neurons in cortex and lower spinal cord brain stem. The etiology pathogenesis ALS are being actively studied, but there still no single concept. study risk factors can help to understand mechanism this development and, possibly, slow down rate its progression patients also reduce people a predisposition toward familial ALS. interest researchers clinicians protective role nutrients has been increasing recent years. However, some them not well-understood or disputed. objective review analyze studies on as environmental affecting developing neuron progression. Methods: We searched PubMed, Springer, Clinical keys, Google Scholar, E-Library databases for publications using keywords their combinations. analyzed all available published 2010–2020. Discussion: 39 studies, including randomized clinical trials, cases, meta-analyses, involving animal models This demonstrated that following vitamins most significant protectors development: vitamin B12, E > C B1, B9 D B2, B6 A, B7. In addition, indicates foods high content cholesterol, polyunsaturated fatty acids, urates, purines plays big part development. Conclusion: inclusion ketogenic diet disease-modifying therapy progression, approach nutrient selection must be personalized. roles C, D, B7 need further study.

Язык: Английский

---

Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives

Cells, Год журнала: 2023, Номер 12(13), С. 1763 - 1763

Опубликована: Июль 1, 2023

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease characterized by the progressive death of motor neurons, leading to paralysis death. It rare high patient-to-patient heterogeneity, which makes its study arduous complex. Extracellular vesicles (EVs) have emerged as important players in development ALS. Thus, ALS phenotype-expressing cells can spread their abnormal bioactive cargo through secretion EVs, even distant tissues. Importantly, owing nature composition, EVs’ formation be exploited for better comprehension this elusive identification novel biomarkers, well potential therapeutic applications, such those based on stem cell-derived exosomes. This review highlights recent advances role EVs etiopathology how promising new strategies.

Язык: Английский

---