Valdor Alonso, Rut

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Valdor Alonso, Rut

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Valdor Alonso, Rut

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular"B" e Inmunología

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Open Access
Dataset of the project: Una Posible Diana Terapeutica para Bloquear la Progresión del Glioblastoma: la Autofagia Mediada por Chaperonas en Pericitos (PID2020-114010RB-I00)
(2026-02-09) Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Valdor Alonso, Rut; Salinas Hidalgo, María Dolores; Bioquímica y Biología Molecular B e Inmunología
Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome
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Effects of living cyanobacteria, cyanobacterial extracts and pure microcystins on growth and ultrastructure of microalgae and bacteria
(Elsevier, 2006-12-02) Aboal Sanjurjo, Marina; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
In this study, we demonstrate the inhibitory effect of both cyanobacterial extracts and pure microcystins on the growth of microalgae and bacteria. This inhibitory effect was more persistent in pure microcystins than in the extracts, which lost their properties eight days after exposure. In addition, the effects on bacteria were longerlasting than those on microalgae. The microalgae exposed to both extracts and cultures of microcystin producing species showed morphological and ultrastructural alterations, even in cases where there was no clear effect on growth. The implications for colonisation and benthic communities structure and development are discussed in the context of biomonitoring.
Open Access
Chaperone-mediated autophagy sustains pericyte stemness necessary for brain tissue homeostasis
(Elsevier, 2025-04-24) Martínez, Carlos M.; Martínez-Morga, Marta; Rodríguez-Madoz, Juan R.; Prósper, Felipe; Zapata, Agustín G.; Moraleda, José María; Martínez, Salvador; García Bernal, David; Roca Soler, Francisco José; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Introduction: Pericytes (PCs) are mural cells exhibiting some mesenchymal stem cell (MSC) properties and contribute to tissue regeneration after injury. We have previously shown that glioblastoma cancer cells induce in PCs, a pathogenic upregulation of chaperone-mediated autophagy (CMA) which modulates immune functions and MSC-like properties to support tumor growth. Objectives: The aim of the study was to interrogate the role of CMA-regulated MSC properties in PCs in the context of tissue repair during inflammation triggered by a demyelinating injury. Methods: Studies of RNA-seq were done PCs with (WT) and without (LAMP-2A KO) CMA. Cell characterization related to stemness, lineage and morphology was done in WT and KO PCs. Secretome analysis and cell differentiation assay using the supernatants from CMA-efficient and deficient PCs cultures was done in mesenchymal cells. Inflammatory response of brain cells was assessed with WT and KO PCs secretome. To corroborate in vitro results, CMA modulation in response to inflammation in PCs and tissue repair markers were measured in the lesion areas of a demyelination mouse model and correlated with the tissue reparation after intravenous PC administration. An inflammatory mediator was used to study effects on PC-CMA activity. Results We found that inflammatory mediators such as IFNγ downregulate CMA in PCs, suppressing PC stemness and promoting a pro-inflammatory secretome. Restoration of PC CMA activity during inflammation maintains PC MSC properties and induces an MSC-like proteome which decreases inflammation and promotes tissue repair. We identified secreted proteins involved in regenerative and protective processes, and therefore, necessary to restore brain tissue homeostasis after inflammation induced by a demyelinating injury. Conclusion: we show that manipulation of CMA activity in host PCs could be a useful therapeutical approach in the context of brain inflammation, which might be extended to other diseases where the pericyte has a key role in response to inflammation.
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Chaperone mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation
(Nature Research, 2014-11) Mocholi, Enric; Botbol, Yair; Guerrero Ros, Ignacio; Dinesh, Chandra; Koga, Hiroshi; Gravekamp, Claudia; Cuervo, Ana María; Macián, Fernando; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation.
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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
(Taylor and Francis Group, Taylor and Francis, 2016-01-21) Klionsky, Daniel J. "et.al."; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
(Taylor and Francis, 2016-01-21) Klionsky, Daniel J.; Abdelmohsen, Kotb ; et al.; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
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Regulación de NFAT por la actividad Poli-ADP Ribosa-Polimerasa en los linfocitos T / Rut Valdor Alonso; directores, José Yélamos López, Pablo Ramírez Romero.
(Murcia : Universidad de Murcia, Departamento de Genética y Microbiología,, 2008) Valdor Alonso, Rut
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Pericytes, a cell type contributing to autoimmunity and immune tolerance
(Elsevier, 2023-06-16) Botía Sánchez, María; Aparicio, Pedro; Valdor Alonso, Rut; Molina Gallego, María Luisa; Bioquímica y Biología Molecular B e Inmunología
Pericytes have been, since their discovery, a very hard-to-define cell because of their unknown ontogeny and the lack of specific markers. As a consequence, several attempts to characterize both its molecular pattern and its metabolism have been carried out to describe the physiological role they play. Pericytes are located in the abluminal wall of small vessels and contribute to the maintenance of capillary tone and the regulation of oxygen flow to adjacent tissues, maintaining the homeostasis of the blood-brain barrier. Furthermore, they have been described as cells with immunological properties, being able to sense and secrete proinflammatory and antiinflammatory cytokines and to activate T cells, hence controlling the immune response. Interestingly, pericytes immune function might be modulated through molecular mechanisms such as chaperone-mediated autophagy, making them to convert from immunogenic to immunosuppressive cells contributing in autoimmunity and immune tolerance. The failure of the different pericytes functions which are implicated in the brain homeostasis is related with several pathologies associated to inflammation, including type 2 diabetes, multiple sclerosis, stroke, Alzheimer's disease, and cancer. In these scenarios, pericytes have always been proved as mediators of the pathology, which indicates that this barely-known type of cell might have a wide variety of unknown roles.
Embargo
The effect of Glioblastoma on Pericytes
(2020-10-29) Molina Gallego, María Luisa; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
Purpose of the Review: Intratumoral pericytes (PC) do not share the same tumor niche as peritumoral PC. Furthermore, glioblastoma multiforme (GB) cells do not seem to affect them equally. Therefore, for a better understanding of the effects of GB on PC, in this chapter, we will classify them according to whether they are intratumoral or peritumoral PC, focusing mainly on peritumoral effects, which seem to have better future prospects for finding effective therapies in GB cancer. Recent Findings: Recently, it has been shown that PC could be the main target of the tumor infiltration front and have a fundamental role in the proliferation, expansion, and survival of the tumor, as well as in the regulation of anti-tumor immune responses. Modulation of the immune function of PC through molecular mechanisms such as chaperone-mediated autophagy (CMA) seems to be essential to prevent an immunosuppressive microenviroment that facilitates tumor growth. Summary: GB is the most frequent and aggressive brain tumor. In the last years, PC have been gaining special attention due to their role in GB progression. GB cells infiltrate away from the tumor core more often and faster when they are associated with perivascular cells. However, to find targeted therapies against PC to promote their brain defense function and improve anti-tumor immune responses requires a better understanding of the heterogeneity, markers, and distribution of PC at origin.
Open Access
Pericytes for use as a medicament
(2023-06-28) Valdor Alonso, Rut; García Bernal, David; Moraleda Jiménez, José María; Martínez Pérez, Salvador; Bioquímica y Biología Molecular B e Inmunología
The present invention refers to a substantially pure population of pericytes, or cell suspension comprising pericytes, wherein the pericytes are at least 80% of the total cell population or suspension, characterized in that CMA is inhibited, for example by inhibiting the expression or deleting the gene LAMP2A. In a preferred embodiment, said population or suspension of pericytes is used as a medicament, for instance in the treatment of cancer, preferably glioblastoma