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Exosome Determinants of Physiological Aging and Age-Related Neurodegenerative Diseases

D’Anca, Marianna, Fenoglio, Chiara, Serpente, Maria, Arosio, Beatrice, Cesari, Matteo, Scarpini, Elio Angelo, Galimberti, Daniela·2019·Frontiers in Aging Neuroscience

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Figure 1 Interaction mechanisms between exosome and recipient cell. Exosomes secreted from a donor cell can move through biological fluids to reach the recipient cell close or distant to the site of their origin. The interaction mechanisms with recipient cell are various: (1) membrane fusion with transfer of exosomal cargo to recipient cell; (2) internalization of whole exosome by endocytosis and release of the cargo by fusion with endosomal membrane; (3) activation of signaling pathways through ligand/receptor interaction. For more details, see review by Jan et al. (2017, 2019).
Figure 1 Interaction mechanisms between exosome and recipient cell. Exosomes secreted from a donor cell can move through biological fluids to reach the recipient cell close or distant to the site of their origin. The interaction mechanisms with recipient cell are various: (1) membrane fusion with transfer of exosomal cargo to recipient cell; (2) internalization of whole exosome by endocytosis and release of the cargo by fusion with endosomal membrane; (3) activation of signaling pathways through ligand/receptor interaction. For more details, see review by Jan et al. (2017, 2019).CC BY · PubMed Central
Figure 2 (A) Exosome structure and cargo. Exosomes are surrounded by a phospholipid bilayer and their content reflects the cell of origin. So besides to generic molecules that identify all exosomes as Tetraspanins, Lipid rafts, MVB formation proteins, membrane transport and fusion proteins, there are other molecules specific to their origin, as L1CAM for neural exosomes as well as proteins related to aging and neurological diseases such as β-amyloid, p-Tau, LRKK2, insulin receptor substrate 1 (IRS-1), a-synuclein, amyloid precursor protein (APP), TDP-43, depeptide protein repeats (DPRs) and many others. In addition, there is also a nucleic component consisting of DNA, mRNA and different kinds of non-coding RNAs (ncRNAs; miRNAs, lncRNAs, circRNAs, piwi-RNA, etc…). (B) Exosomes: a double-edged sword in neurodegenerative disease. Exosomes could favorite and/or trigger the spreading of the disease leading to neurodegeneration or they could sequester neuro-toxic components from neural cells protecting them.
Figure 2 (A) Exosome structure and cargo. Exosomes are surrounded by a phospholipid bilayer and their content reflects the cell of origin. So besides to generic molecules that identify all exosomes as Tetraspanins, Lipid rafts, MVB formation proteins, membrane transport and fusion proteins, there are other molecules specific to their origin, as L1CAM for neural exosomes as well as proteins related to aging and neurological diseases such as β-amyloid, p-Tau, LRKK2, insulin receptor substrate 1 (IRS-1), a-synuclein, amyloid precursor protein (APP), TDP-43, depeptide protein repeats (DPRs) and many others. In addition, there is also a nucleic component consisting of DNA, mRNA and different kinds of non-coding RNAs (ncRNAs; miRNAs, lncRNAs, circRNAs, piwi-RNA, etc…). (B) Exosomes: a double-edged sword in neurodegenerative disease. Exosomes could favorite and/or trigger the spreading of the disease leading to neurodegeneration or they could sequester neuro-toxic components from neural cells protecting them.CC BY · PubMed Central
Figure 3 Exosomes are able to pass through blood brain barrier (BBB) in both directions. This means that specific exosomes (i.e., the neural ones with L1CAM on their surface) detected in the cerebrospinal fluid (CSF) can be released into bloodstream and vice versa. This feature makes exosomes appealing in the research of new sources of biomarkers suitable for use in clinical practice, as liquid biopsy that could replace current invasive diagnostic methods.
Figure 3 Exosomes are able to pass through blood brain barrier (BBB) in both directions. This means that specific exosomes (i.e., the neural ones with L1CAM on their surface) detected in the cerebrospinal fluid (CSF) can be released into bloodstream and vice versa. This feature makes exosomes appealing in the research of new sources of biomarkers suitable for use in clinical practice, as liquid biopsy that could replace current invasive diagnostic methods.CC BY · PubMed Central
Figure 4 Comprehensive expression profile patterns of ncRNAs differentially expressed in patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Parkinson’s disease (PD) extracted from serum or CSF exosomes.
Figure 4 Comprehensive expression profile patterns of ncRNAs differentially expressed in patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Parkinson’s disease (PD) extracted from serum or CSF exosomes.CC BY · PubMed Central

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Authors
D’Anca, M., Fenoglio, C., Serpente, M., Arosio, B., Cesari, M., Scarpini, E. A., & Galimberti, D.
Venue
Frontiers in Aging Neuroscience
Published
2019-08-28
Volume
11
ISSN
1663-4365
Cited by
154
References
20
Funders
Ministero della Salute

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