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Speaker at International Alzheimer’s Disease & Dementia Conference 2022 - Izaskun Buendia
University of Santiago de Compostela, Spain
Title : Neddylation is Essential for Oligodendrocyte Differentiation and Myelination Process


The myelin sheaths that cover the axons are essential for the conduction of nerve impulses in the nervous system. In this regard, mature oligodendrocytes are the myelinating cells of the central nervous system (CNS). In recent decades, research on the mechanisms involved in myelination has generally focused on transcriptional ones, whereas post-translational ones remain mainly unknown. In this line, neddylation, an ubiquitylation-like pathway that conjugates an ubiquitin-like protein NEDD8 to target proteins, has emerged as a critical regulatory process controlling ubiquitination, protein transcription and signalling transduction. Dysregulation of neddylation has been recently linked to CNS pathological conditions, including epilepsy and multiple sclerosis. On this basis, our aim is to study the role of neddylation in oligodendrocytes and, consequently, in myelination. For this purpose, we used MLN4924 (Pevonedistat), an FDA- and EU-designated Orphan Drug, an inhibitor that acts on NAE, the initiating enzyme in the neddylation cascade. First, we studied its effect during development, by injecting MLN intraperitoneally into rats from postnatal day 7 to 15. In the brain and spinal cord of these rats, there was a significant impairment of the expression of proteins present in the membrane of myelinating oligodendrocytes, such as MBP and MAG. Likewise, in MLN-treated cortical oligodendrocyte cultures, the inhibition of neddylation caused a significant decrease in cell viability and the expression of MBP and MAG, among others. Together, these results indicate that neddylation inhibition compromises both the viability and the level of differentiation and maturation of oligodendrocytes, and may negatively affect the formation and maintenance of myelin sheaths in the CNS. These findings shed light on the post-translational mechanisms involved in myelination and lay the groundwork for future studies on the role of neddylation in degenerative diseases.

What will audience learn from your presentation?

  • Neddylation is essential for not only neural development but also for glial development.
  • Its disruption leads to different neurodenerative diseases
  • Neddylation can be involved in different pathological conditions discussed in the conference
  • It can be pharmacologically and genetically inhibited, affording a good tool for its study.


Dr. Buendia studied Biology at the Universidad Complutense de Madrid and performed master’s studies in “Pharmacological research” at Universidad Autónoma de Madrid in 2011. After she joined the research group of Prof. G. López. In 2015 she received her PhD degree with National award. After two years of postdoctoral contract (Spanish Minsitry), when she performed two international stays in Caen, France, with independent funding’s, she spent one more year there. After, she returned to Spain thanks to a postdoctoral contract from the Spanish Ministry (Juan de la Cierva Incorporación) and joined the Gene Regulatory Control in Disease Laboratory, CIMUS, led by Dr. Whoodhoo. She has published more than 35 research articles in SCI journals; she participates in the teaching activities and co-directs a PhD student.