From corpora amylacea to wasteosomes
[eng] Corpora amylacea (CA) in the human brain are polyglucosan aggregates that were first described by J.E. Purkinje in 1837. They are intracellular astrocytic bodies that accumulate mainly in perivascular, periventricular and subpial regions of the aging brain, but are also present in large number...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/189683 |
| Acceso en línea: | https://hdl.handle.net/2445/189683 http://hdl.handle.net/10803/675598 |
| Access Level: | acceso abierto |
| Palabra clave: | Envelliment Malalties neurodegeneratives Immunitat Aging Neurodegenerative Diseases Immunity |
| Sumario: | [eng] Corpora amylacea (CA) in the human brain are polyglucosan aggregates that were first described by J.E. Purkinje in 1837. They are intracellular astrocytic bodies that accumulate mainly in perivascular, periventricular and subpial regions of the aging brain, but are also present in large numbers in specific areas of the brain in neurodegenerative conditions. Different studies suggest that the function of CA seems to be directed towards trapping products derived from aging or degenerative processes. While essentially constituted of polymerized hexoses, primarily glucose, a wide range of components have been described in CA, some of them derived from neurons, astrocytes, oligodendrocytes or blood, or even related to viral, fungal or microbial infections. Their location in the perivascular, periventricular and subpial regions of the brain, all of them connected or close to cavities filled with cerebrospinal fluid (CSF), suggests that CA can be extruded from these regions into the CSF. Furthermore, CA contain neo-epitopes (NE) of an unknown nature that are recognized by natural antibodies of IgM type. This IgM-NE interaction indicates that if CA were released from the central nervous system (CNS), they could interact with the natural immune system, which could intervene in their elimination. This body of evidence allowed us to consider that CA not only entrap residual products, but also act as waste containers involved in a cleaning mechanism that removes residual substances from the CNS. Accordingly, this thesis aimed to verify this hypothesis. Our studies revealed the presence of CA in the CSF and in the cervical lymph nodes, into which CSF drains through the meningeal lymphatic system. In the cervical lymph nodes, we observed CA making contact with certain cells that, according to their location, shape, and staining properties may be macrophages. Subsequent in vitro studies showed that CA are phagocytosed and degraded by macrophages. We also observed that there may be redundant mechanisms involved in triggering the phagocytosis process, which would ensure the elimination of CA. Moreover, these mechanisms are related to non-inflammatory responses, which allow the elimination of CA without tissue damage. On the other hand, we pointed out that the NE present in CA, which may act as “eat-me” signals that would enhance the phagocytosis of CA, have a carbohydrate nature. Taken together, these findings support the above-mentioned hypothesis, indicating that CA can act as containers that remove waste products from the brain and are involved in a mechanism that cleans the CNS. According to these results, the present thesis was later extended to find out the function of the CA from other organs and tissues. In this regard, we aimed to establish a global and integrative hypothesis about the function and significance of CA in the whole organism. The results allowed us to suggest that CA in the different organs are created by specific cells, which collect waste products and amass them within a glycan structure, and secrete them into the external medium or interstitial spaces being, in this second case, phagocytosed by macrophages. Overall, we suggested considering CA from the different tissues of the human body as waste containers. Lastly, to avoid the ambiguity of the terms amyloid or amylacea (that indicate starch-like structures but can also refer to insoluble fibrillary proteins), we proposed renaming CA as “wasteosomes”, emphasizing the waste products they entrap rather than their misleading amyloid properties. |
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