CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOACaptura de pantalla 2022 09 14 a las 10.27.10    

Lipids in neuronal physiology and pathology

Research summary:

Our laboratory is interested in understanding the role of lipids in neuronal physiology and pathology focusing on their participation in synapses. In recent years our knowledge about the protein machinery that controls synaptic transmission has greatly increased. However, much less is known about the contribution of lipids to this process despite the fact that binding to the membrane, of which lipids are major components, modulates the activity of essential synaptic proteins. Moreover, synaptic transmission relies on membrane dynamics. The observation that most lipidosis lead to cognitive impairment and mental retardation further support the relevance of lipids in such process. We focus on the analysis of sphingolipids and cholesterol because, among other reasons, they are particularly enriched in neurons and have the ability to form signalling platforms. As experimental models we use mice in which enzymes related to lipid metabolism or lipid transport proteins have been genetically altered allowing in vivo analysis. These mice mimic fatal lysosomal storage disorders, such as Niemann pick type A and C, which lead to cognitive and psychiatric problems, neurodegeneration and early death. Interestingly, the lipidic alterations we have found in these mice are similar to those reported in aging brains. This opens the possibility that our results will have implications not only in the establishment and maintenance of synapses but also in their functional decay during aging. Therefore, we hope our work will contribute to understand and treat neurological diseases in childhood as well as neurodegenerative disorders like Alzheimer's disease.


Figure 1: The figure exemplifies the drastic effects that changes in sphingolipid levels have in synapses. Electron microscopy analysis in the hippocampus of age-matched wild type and acid sphingomyelinase knockout mice evidence a significant size reduction of the pre and postsynaptic compartments in the mutant animals, which show high levels of sphingomyelin and its derivatives.


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Gaudioso GuiradoÁngel2024597angel.gaudioso(at)cbm.csic.esInvestigador
Guerrero ValeroMarta2024535mguerrero(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Ledesma MuñozMaría Dolores2024535dledesma(at)cbm.csic.esE. Investigadores Científicos de Organismos Públicos
Melgarejo de la PeñaElena2024597/4535emelgarejo(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1
Moreno HuguetPilar2024535Estudiante TFG
Naya ForcanoSara2024597snaya(at)cbm.csic.esInvestigador Indef. GP1
Soto HuelinBeatriz2024597beatriz.soto(at)cbm.csic.esAyudante Investigación
Toledano ZaragozaAna2024597atoledano(at)cbm.csic.esInvestigador

Relevant publications:

  • M.D. Ledesma, M.G. Martin, C.G. Dotti. Lipid changes in the aged brain: effect on synaptic function and neuronal survival. (2012) Prog. Lipid Res. 51: 23-35.
  • A.I. Arroyo, P.G. Camoletto, L. Morando, M. Sassoe-Pognetto, M. Giustetto, P.P. Van Veldhoven, E.H. Schuchman, M.D. Ledesma “Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a mouse model for Niemann Pick disease type A”. (2014) EMBO Mol Med 6(3):398-413.
  • E. Gabandé-Rodriguez, P. Boya, V. Labrador, C.G. Dotti, M.D. Ledesma. High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A. (2014) Cell Death & Diff. 21:864-875.
  •  A. Franco-Villanueva, E. Fernández-López, E. Gabandé-Rodríguez, I. Bañón-Rodríguez, J.A. Esteban, I.M. Antón, M.D. Ledesma. WIP modulates dendritic spine actin cytoskeleton by transcriptional control of lipid metabolic enzymes. (2014) Hum. Mol. Genet. 15:4383-4395.
  • A. Pérez-Cañamás, S. Sarroca, C. Melero-Jerez, D. Porquet, J. Sansa, S. Knafo, J.A. Esteban, C. Sanfeliu, M.D. Ledesma. Neurobiol Aging. (2016) 48:1-12.
  • A.Pérez-Cañamás, S. Benvegnù, C.B. Rueda, A. Rábano, J. Satrústegui, M.D. Ledesma.Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease. Mol Psychiatry. (2017) 22: 711-723.
  • Gabandé-Rodríguez E, Pérez-Cañamás A, Soto-Huelin B, Mitroi DN, Sánchez-Redondo S, Martínez-Sáez E, Venero C, Peinado H, Ledesma MD.Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders. EMBO J. (2019) 38 (2): 1-22.
  • L.Samaranch, A. Pérez-Cañamás, B. Soto-Huelin, V. Sudhakar, J. Jourado-Arjona, P. Hadaczek, J. Ávila, J.R. Bringas, J. Casas, H. Chen, X.He, E.H. Schuchman, S.H. Cheng, J. Forsayeth, K.S. Bankiewicz, M.D. Ledesma. Adeno-associated viral vector serotype 9-based gene therapy for Niemann Pick disease type A. Science Transl Med. (2019) 11 (506).
  • D.N. Mitroi, G. Pereyra-Gómez, B. Soto-Huelin, F. Senovilla, T. Kobayashi, J.A. Esteban, M.D. Ledesma. NPC1 enables cholesterol mobilization during long-term potentiation that can be restored in Niemann-Pick disease type C by CYP46A1 activation. EMBO Rep. (2019) e48143.

Doctoral theses:

  • Estefanía Fernández López. “Influencia de WIP en el citoesqueleto de actina y la composición lipídica de las espinas dendríticas”, Junio 2013, Universidad Autónoma Madrid. Sobresaliente Cum laude. Directores: María Dolores Ledesma, Inés Antón.
  • Enrique Gabandé Rodríguez. “Alteraciones de la autofagia mediadas por la acumulación de esfingomielina en la enfermedad de Niemann Pick tipo A”, Julio 2014 Universidad Autónoma Madrid. Sobresaliente Cum laude. Directores: María Dolores Ledesma, Carlos Dotti.
  • Cristian Galván. “Relevancia de los rafts en la polaridad neuronal e implicancias de sus alteraciones en la enfermedad de Niemann Pick tipo A”, Agosto 2014 Universidad Católica de Córdoba, Argentina. Sobresaliente Cum laude. Directores: María Dolores Ledesma, Dante Beltramo.
  • Ana Isabel Arroyo Tejedor. “Caracterización y rescate de las anomalías en espinas dendríticas en un modelo murino para la enfermedad de Niemann Pick tipo A”, Octubre 2014  Universidad Autónoma Madrid. Sobresaliente Cum laude. Directora: María Dolores Ledesma.
  • Azucena Pérez Cañamás. “Alteraciones de la homeostasis de calcio y esters oxidativo en neuronas deficientes en la esfingomielinasa ácida. Implicaciones en la enfermedad de Niemann Pick tipo A. Junio 2015 Universidad Autónoma Madrid. Sobresaliente Cum laude. Directora: María Dolores Ledesma.
  • Adrián Bartoll Andrés. “El sistema endocannabinoide en la patología y terapia de la enfermedad de Niemann Pick tipo A”, Mayo 2019, Universidad Autónoma Madrid. Sobresaliente Cum laude. Directora: María Dolores Ledesma.


  • Methods and compositions for treatment of Alzheimer’s disease by enhancing plasmin or plasmin-like activity”. Inventores: M.D.Ledesma, C.G.Dotti. No. 09/502,448/ 2000, Julio 2000.
  • Method for the treatment of Niemann Pick disease type A and related neurological disorders through the activation of neutral sphingomyelinase. Inventores: A.I. Arroyo, P.G. Camoletto, M.D. Ledesma. Oficina española de patentes No. P201131297, Julio 2011.
  • Compositions and methods for activating signaling through the CB1 cannabinoid receptor for treating and preventing diseases and disorders characterized by abnormal celular accumulation of sphingolipids such as sphingomyelin. Inventores: M.D. Ledesma, A. Bartoll, E.H.Schuchman. US patent office Application number: 62638837, Marzo 2018.
  • Use of Efavirenz for the treatment of Lipid Storage Diseases. Inventores: D.N. Mitroi, M.D. Ledesma. Oficina española de patentes No: P201830486, Mayo 2018.

NOTE! This site uses cookies and similar technologies.

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

I understand


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: