期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms222212288
关键词
extracellular vesicles; disease spreading; neurodegenerative diseases; polyglutamine diseases; vehicle; biomarker
资金
- European Regional Development Fund (ERDF) through the Centro 2020 Regional Operational Programme under BrainHealth2020 projects, through the COMPETE 2020Operational Programme for Competitiveness and Internationalization [CENTRO-01-0145-FEDER-000008]
- FCTFundacao para a Ciencia e a Tecnologia [UIDB/04539/2020, POCI-01-0145-FEDER-030737, PTDC/BTM-ORG/30737/2017, CEECIND/04242/2017, 2020.04751.BD]
- National Ataxia Foundation
- French Muscular Dystrophy Association (AFM-Telethon) Trampoline Grant [20126]
- Richard Chin and Lily Lock MachadoJoseph Disease Research Fund
- JPND project SynSpread
- Fundação para a Ciência e a Tecnologia [PTDC/BTM-ORG/30737/2017, 2020.04751.BD] Funding Source: FCT
Recent research has shown that disease-causing proteins can spread from one focal point to other regions in the brain through extracellular vesicles. These vesicles, carrying pathological molecules, may trigger pathological pathways when internalized by healthy cells, ultimately promoting disease spread to neighboring cells.
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.
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