Abstract
Recent research demonstrated pathological spreading of the disease-causing proteins from one focal point across other brain regions for some neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. Spreading mediated by extracellular vesicles is one of the proposed disease-spreading mechanisms. Extracellular vesicles are cell membrane-derived vesicles, used by cells for cell-to-cell communication and excretion of toxic components. Importantly, extracellular vesicles carrying pathological molecules, when internalized by “healthy” cells, may trigger pathological pathways and, consequently, promote disease spreading to neighboring cells. Polyglutamine diseases are a group of genetic neurodegenerative disorders characterized by the accumulation of mutant misfolded proteins carrying an expanded tract of glutamines, including Huntington’s and Machado–Joseph disease. The pathological spread of the misfolded proteins or the corresponding mutant mRNA has been explored. The understanding of the disease-spreading mechanism that plays a key role in the pathology progression of these diseases can result in the development of effective therapeutic approaches to stop disease progression, arresting the spread of the toxic components and disease aggravation. Therefore, the present review’s main focus is the disease-spreading mechanisms with emphasis on polyglutamine diseases and the putative role played by extracellular vesicles in this process.
Highlights
Nanotubes, which aremechanisms tunnel-like membrane-derived structures that connect two cells allowing the direct exchange of biomolecules; (B) extracellular vesicles that are membrane-derived vesicles secreted by cells with part of their cellular different mechanisms through which the disease-causing proteins/RNAs may spread from cell to cell: (A)
Nanotubes, which are tunnel-like membrane-derived structures that connect two cells allowing the direct exchange of content, which can spread and deliver their content to distant cells; (C) soluble oligomers, which due to their small size biomolecules; (B) extracellular vesicles that are membrane-derived vesicles secreted by cells with part of their cellular may be able to escape the cell and spread to the extracellular milieu, and (D) synaptic connection, a highly effective content, which can spread and deliver their content to distant cells; (C) soluble oligomers, which due to their small size communication pathway that may be responsible for the transmission of disease-causing proteins between neurons
In the past years it has been proposed that interneuronal seeding and spreading of disease-associated molecules occurs in several neurodegenerative diseases, analogous to the prion seeding mechanism present in Prions disease
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In the late 1990s did two publications project EVs again in the spotlight, describing them, for the first time, as being crucial for intercellular communication, namely in B lymphocytes and Dendritic Cells (DC’s) [7,8]. In these studies, the presence of Major. Analyzing the literature, EVs are described to be released by all cell types and can be found in biofluids, such as milk, saliva, blood, urine, and semen [1,11,12,13] These particles carry proteins, lipids, and RNAs that might be used as biomarkers for diseases. The hypothesis that mutated proteins and their cleaved fragments or mutant mRNAs are spread across the brain via EVs is building evidence [16]
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