Molecular mechanisms of neurodegeneration

Research summary:

Our group is mostly interested in neurodegenerative disorders is now focusing in a group of brain disorders associated with aging, such as Alzheimer, disease and some type of brain tumours. A question that remains open is... are there common molecular mechanisms that underlie the age dependence of various disorders? Data from different animal models strongly support that idea that the PI3K-Akt pathway is deregulated in several brain pathologies.

With respect to AD, our previous work has led us to analyze some elements regulated by Akt, such as mTORC1. This protein complex controls general aspects of protein synthesis and autophagy; while his dysfunction has been considering a key factor in the generation and / or degradation of beta amyloid in Alzheimer's disease (AD). We are analyzing how the activity of mTORC1 modulates macro-autophagy, and how it modulates the generation of amyloid peptide in transgenic models of AD.

With regard to astrocyte-astrocytoma-gliomas tumor transformation, we have defined a new route of tumor progression and maintenance of stem-tumor phenotype, via Akt, WIP and YAP / TAZ that regulate this conversion [Collaboration: F. Wandosell (CBM) &. Dr. I. Anton (CNB)]. In addition, in both pathologies we are interested in defining new therapeutic targets and analyzing new compounds with therapeutic potential.

The last year (2016) Drª: Beatriz Cubelos (RyC/ Assist. Prof) has been incorporated as Project Leader in our lab, and is currently analyzing the phenotype of RRas1 and RRas 2 knockout mice, which among other anomalous features have defect in myelination and a deficient signaling in Akt. We have initiated a collaborative work analyzing the defective mechanism/s in both RRas mutants.

Drª B. Cubelos’ group demonstrate that R-Ras1 and R-Ras2 play essential roles in regulating myelination “in vivo” and control fundamental aspects of oligodendrocyte (OL) survival and differentiation through synergistic activation of PI3K/Akt and Erk1/2-MAPK signaling. Mice lacking R-Ras1 and/or R-Ras2 show a diminished OL population with a higher proportion of immature OLs, explaining the observed hypomyelination and provoking a slower conduction velocity of nerve impulses in main CNS tracts. She is now an independent group and you can check the specific information on their website.

Image

Figure 1.

Image

* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
García JuanMarta2064591martagajuan(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Martín MartínezLaura2064591Estudiante TFM
Neves MartínElena2064591elena.neves(at)cbm.csic.esInvestigador
Orantes FernandezAlba2134425alba.orantes(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Ordoñez GutiérrezLara2064591lordoniez(at)cbm.csic.esContratado CIBER
Pérez AlvarezMaría José2064591Profesor Contratado Universidad, GA
Villa GonzálezMario2064591mario.villa(at)cbm.csic.esTitulado Sup.de Actividades Técn. y Profes. GP1
Wandosell JuradoFrancisco2064561fwandosell(at)cbm.csic.esE. Profesores de Investigación de Organismos Públicos de Investigación

Relevant publications:

  • Ordóñez-Gutiérrez L, Posado-Fernández A, Ahmadvand D, Lettiero B, Wu L, Antón M, Flores O, Moghimi SM, Wandosell F. (2017). “ImmunoPEGliposome-mediated reduction of blood and brain amyloid levels in a mouse model of Alzheimer’s disease is restricted to aged animals” Biomaterials.112:141-152 , doi: 10.1016/j.biomaterials.2016.07.027
  • Escoll M, Gargini RA, IM Anton*, Wandosell F*. (2017). “Mutant p53 oncogenic functions in cancer stem cells are regulated by WIP through YAP/TAZ”. Oncogene;36(25):3515-3527. doi: 10.1038/onc.2016.518.
  • Irene Benito-Cuesta, Héctor Diez, Lara Ordoñez and Francisco Wandosell (2017)” Assessment of autophagy in neurons and in brain tissue.” Cells, 6: 3; doi: 10.3390/cells6030025
  • Inés Anton, Carla Gomez-Oro, Sergio Rivas and Francisco Wandosell (2018). “Crosstalk between WIP and Rho family GTPases" : Small GTPases 1-7(Epub 2018 Jan 29) doi: 10.1080/21541248.2017.1390522
  • Lara Ordóñez-Gutiérrez, Irene Benito-Cuesta, José Luis Abad, Josefina Casas, Gemma Fabrias and Francisco Wandosell .(2018). "Dihydroceramide desaturase 1 inhibitors reduce amyloid-β levels in primary neurons from an Alzheimer's disease transgenic model" Pharmaceutical Research 35:3-49 doi 10.1007/s11095-017-2312-2  
  • Dario Carradori, Claudia Balducci, Davide Brambilla, Francesca Re, Benjamin Le Droumaguet, Fabio De Nicolo, Tatiana Rozzi, Orfeu Flores, Alice Gaudin, SimonaMura, Valérie Nicolas, Gianluigi Forloni, Lara Ordoñez-Gutierrez, Francisco Wandosell, Massimo Masserini, Julien Nicolas, Patrick Couvreur, and Karine Andrieux. (2018). “Antibody-Functionalized Polymer Nanoparticle Leading to Memory Recovery in Alzheimer's Disease-like Transgenic Mouse Model” Nanomedicine:Nanotechnology, Biology, and Medicine 14:2-609-618. doi: 10.1016/j.nano.2017.12.006.
  • Ángel Enrique Céspedes Rubio*, Maria José Pérez-Alvarez*, Catalina Lapuente Chala and Francisco Wandosell. (2018). “ Sex steroid hormones as neuroprotective elements in ischemia models” J. Endocrinol.;237(2):R65-R81. doi: 10.1530/JOE-18-0129.
  • Perez-Alvarez, M. J.; Villa Gonzalez, M.; Benito-Cuesta, I. and Wandosell, F. G (2018) Role of mTORC1 Controlling Proteostasis after Brain Ischemia. Front Neurosci. 12: 60; doi : 10.3389/fnins.2018.00060
  • Rivas, S., Gomez-Oro, C., Anton, I. M. and Wandosell, F. (2108) “Role of Akt Isoforms Controlling Cancer Stem Cell Survival, Phenotype and Self-Renewal” Biomedicines 6: 1; doi: 10.3390/biomedicines6010029
  • Jose L. Herrera, Lara Ordoñez-Gutierrez , Gemma Fabrias , Josefina Casas , Araceli Morales , Guadalberto Hernandez , Nieves G. Acosta5, Covadonga Rodriguez , Luis Prieto-Valiente, Luis M. Garcia-Segura*, Rafael Alonso* and Francisco G. Wandosell * (2018). "Ovarian function modulates the effects of long-chain polyunsaturated fatty acids on the mouse cerebral cortex", Frontiers in Neuroscience; 12:103. doi: 10.3389/fncel.2018.00103. eCollection
  • Sergio Rivas, Inés M. Antón, and Francisco Wandosell (2018) “WIP‐YAP/TAZ as a new pro‐oncogenic pathway in glioma”. Cancers 10:6 , doi: 10.3390/cancers10060191
  • Miriam Sanz-Rodriguez, Juan Escudero-Ramirez, Fernando de Castro, Agnès Gruart, José María Delgado-García, Francisco Wandosell and Beatriz Cubelos*. (2018) "R-Ras1 and R-Ras2 are essential for oligodendrocyte differentiation and survival for correct myelination in the central nervous system," The Journal of Neuroscience (2018) 38(22):5096 –5110. doi: 10.1523/JNEUROSCI.3364-17.2018
  • Sergio Rivas, Inés M. Antón, and Francisco Wandosell (2018) WIP‐YAP/TAZ as a new pro‐oncogenic pathway in glioma. Cancers 2018, 10(6), 191;doi.org/10.3390/cancers10060191

Doctoral theses:

  • Irene Benito Cuesta, “Análisis de las vías de inducción de Autofagia en neuronas y su papel neuroprotector en un modelo transgénico de la enfermedad de Alzheimer“, Sobresaliente Cum Laude, Universidad Autónoma de Madrid, Facultad de Ciencias,  26/07/2017, Director: Dr. Francisco Wandosell.

Ongoing projects:

  • Programme I+D+i-RETOS- RTI2018-096303-B-C1. “Papel de la vía AKT/YAP/TAZ en Patologías del Sistema Nervioso Central”. (2019-2021) IP1- Francisco Wandosell;  IP2- Inés M. Antón Gutiérrez
  • ISCIII-CIBERNED –Proyectos Colaborativos- PI2016/01”- (2017-2018)- Coordinador .Dr. I.Torres-Aleman
  • Fundación RAMON ARECES -Proyectos de investigación en Ciencias de la Vida y de la Materia, correspondientes al XVIII Concurso Nacional. (2018-20). IP. Drª. Ines M. Anton ;  coIP  Francisco Wandosell (CIBERNED)
  • CAM-Biomedicina 2017, B2017/BMD-3700; “BASES METABÓLICAS DE LA NEURODEGENERACIÓN” (NEUROMETAB-CM)-Coordinador: Dr. Gonzalez Castaño, Jose (UAM);IP .Dr. F. Wandosell (CBM-CSIC)
  • RETOS-COLABORACION 2017-2019 (RTC2017-5994-1). “Fármacos Innovadores para el tratamiento de la Enfermedad de Alzheimer: Estudios preclínicos de la eficacia y toxicidad bajo condiciones BLP por vía oral”  Coordinador: ALLINKY BIOPHARMA SL; IP- CBM-CSIC: F Wandosell.

EU projects:

  • COST-EU Framework Prog. H2020- “European Network of Multidisciplinary Research and Translation of Autophagy knowledge” TRANSAUTOPHAGY COST ACTION CA15138, (ref. OC-2015-1-19840).
  • ERA-NET NEURON 2016 (PCIN-2016-108) “Regulacion del reflejo de micción después de lesiónmédular: abolición por silenciamiento de losaferentes de las fibras C de la vejiga hiper-excitados mediante terapia génica para restaurar la continencia y la micción”-ELPIS". Coordinator: Pr. François Giuliano (Francia); PI-(CBM-CSIC): F Wandosell (Spain)

Teaching activities:

  • Máster en Biomedicina Molecular. Departamento de Biología Molecular y de Bioquímica (UAM). Módulo: ENFERMEDADES NEUROLÓGICAS (BMM6) (2014-2019) Coordinadores: Dr. Javier Díaz Nido (Dpto. Biología Molecular UAM), Dr. Francisco Wandosell  (CBMSO, CSIC-UAM).

Others:

  • Our group belong to Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED): PI - F Wandosell

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: