Our lab focuses on two main research lines: 1) to decipher the contribution of glial cells to intra-axonal protein synthesis through horizontal transfer of extracellular vesicles in physiological and pathological conditions (e.g experimental models of Alzheimer’s disease) and 2) to unravel the role of local protein synthesis in glia (e.g oligodendrocytes, microglia…) in the healthy and the diseased brain.
Axons are able to respond to changes in their environment by producing proteins locally. Intra-axonal protein synthesis plays relevant roles in growth cone behavior and synapse formation during embryonic development, and in axon maintenance by regulating mitochondrial function in adulthood. Importantly, a role for local translation in mediating amyloid-induced neurodegeneration, a hallmark for Alzheimer´s disease, has recently been described. Although most localized mRNAs are believed to be transported to distal axons from the somatodendritic compartment, recent evidence suggests that some axonal transcripts might be delivered to axons by glial cells. Among the mechanisms proposed for this horizontal transfer, is the secretion of RNA-containing extracellular vesicles (EVs) by glia and subsequent internalization into axons. Our aim is to determine the contribution of glial EVs in the ability of axons to translate proteins locally in models of amyloid-induced pathology. Ultimately, we wish to understand if EVs play a role in neurological disorders such Alzheimer´s disease, by regulating intra-axonal signaling events that require local translation.
Dysregulation of localized translation and its potential contribution to disease progression has been only recently acknowledged. However, most of the research on local protein synthesis in Alzheimer´s disease have been performed in neurons. We recently became interested in unraveling the role of local translation in glia itself in the physiology and the pathophysiology of the nervous system.
Primary neuronal and glial cultures; neuron-glia co-cultures; Animal models of Alzheimer´s disease; Isolation of extracellular vesicles; Cellular and Molecular Biology techniques to measure RNA localization and local translation: in situ hybridization; SUnSET; proximity liogation assays.
CREB3L2-ATF4 heterodimerization defines a transcriptional hub of Alzheimer’s disease gene expression linked to neuropathologyScience Advances (Mar, 2023) DOI: 10.1126/sciadv.add2671
Local Translation in Nervous System PathologiesFrontiers in Integrative Neuroscience (Jun, 2021) DOI: 10.3389/fnint.2021.689208