Beatriz Alvarez-Castelao Lab
Understanding Neurodegeneration
Biography
I have worked in science since 2001, starting at USAL where I worked in yeast to obtain my DEA (similar to Master’s). After, I moved to the UAM for my PhD and first Post-doc, working in proteins related with familiar Parkinson Disease. Continuing with my interest in studying the nervous system I moved to Frankfurt for my postdoc. Now I am in the UCM and continue working in neurodegenerative diseases.
Current Projects
Parkinson’s Disease
We have two projects on Parkinson Disease, one in collaboration with Erin Schuman (MPI-BR) in which we are studying the dopaminergic proteome and how it is altered in disease models. The second project is in collaboration with José González (UAM) in which we are investigating a protein related with familiar PD; DJ-1.
Huntington’s Disease
We are investigating how aggregates of the same protein
-Huntingtin- differentially affect diverse brain cell-types.
tRNA Expression
In collaboration with Erin Schuman, Julio D. Perez and Armando Reyes, we are investigating the role of tRNAs in neurodegenerative diseases.
People
Present Students
Rodrigo Alvarez Pardo- PhD student
Daniela Castro Guarderas- Master’s
Daniel Ouro Corredera- Master’s
Adrian Egosa Guillen- Graduate student
Former Students
María Marco Aisa- Master’s
Grants and Prices
Present Grants
PID2020-113270RA-I00
2019T1/BMD-14057
RYC2018-024435-I
Past Grants
Marie Curie IEF
Prices
Scientific Discovery Price- Max Planck Institute for Brain Research (Frankfurt)
Best Scientific paper of the year- IdiPaz (Madrid)
Publications
Giandomenico, S. L., Alvarez-Castelao, B. & Schuman, E. M. Proteostatic regulation in neuronal compartments. Trends Neurosci. 45 (1), 41-52, (2022).
Di Lauro, C. et al. P2X7 receptor blockade reduces tau induced toxicity, therapeutic implications in tauopathies. Prog Neurobiol. 208 102173, (2022).
Spaulding, E. L. et al. The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy. Science. 373 (6559), 1156-1161, (2021).
Perez, J. D. et al. Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons. Elife. 10, (2021).
Dorrbaum, A. R., Alvarez-Castelao, B., Nassim-Assir, B., Langer, J. D. & Schuman, E. M. Proteome dynamics during homeostatic scaling in cultured neurons. Elife. 9, (2020).
Alvarez-Castelao, B. et al. The switch-like expression of heme-regulated kinase 1 mediates neuronal proteostasis following proteasome inhibition. Elife. 9, (2020).
Alvarez-Castelao, B., Schanzenbacher, C. T., Langer, J. D. & Schuman, E. M. Cell-type-specific metabolic labeling, detection and identification of nascent proteomes in vivo. Nat Protoc. 14 (2), 556-575, (2019).
Alvarez-Castelao, B, Schanzenbächer, C.Dieck, S.T. Langer JD, Schuman EM. Zelltypspezifische Proteommarkierung in vivo, Biospektrum, (2018).
Sambandan, S. et al. Activity-dependent spatially localized miRNA maturation in neuronal dendrites. Science. 355 (6325), 634-637, (2017).
Alvarez-Castelao, B. et al. Cell-type-specific metabolic labeling of nascent proteomes in vivo. Nat Biotechnol. 35 (12), 1196-1201, (2017).
Sanchez-Lanzas, R. et al. Protein degradation in a LAMP-2-deficient B-lymphoblastoid cell line from a patient with Danon disease. Biochim Biophys Acta. 1862 (8), 1423-1432, (2016).
Hanus, C. et al. Unconventional secretory processing diversifies neuronal ion channel properties. Elife. 5, (2016).
Alvarez-Castelao, B. & Schuman, E. M. The Regulation of Synaptic Protein Turnover. J Biol Chem. 290 (48), 28623-28630, (2015).
Alvarez-Castelao, B., Gorostidi, A., Ruiz-Martinez, J., Lopez de Munain, A. & Castano, J. G. Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls. Front Aging Neurosci. 6 169, (2014).
Alvarez-Castelao, B., Goethals, M., Vandekerckhove, J. & Castano, J. G. Mechanism of cleavage of alpha-synuclein by the 20S proteasome and modulation of its degradation by the RedOx state of the N-terminal methionines. Biochim Biophys Acta. 1843 (2), 352-365, (2014).
Alvarez-Castelao, B., Losada, F., Ahicart, P. & Castano, J. G. The N-terminal region of Nurr1 (a.a 1-31) is essential for its efficient degradation by the ubiquitin proteasome pathway. PLoS One. 8 (2), e55999, (2013).
Alvarez-Castelao, B., Ruiz-Rivas, C. & Castano, J. G. A critical appraisal of quantitative studies of protein degradation in the framework of cellular proteostasis. Biochem Res Int. 2012 823597, (2012).
Alvarez-Castelao, B. et al. Reduced protein stability of human DJ-1/PARK7 L166P, linked to autosomal recessive Parkinson disease, is due to direct endoproteolytic cleavage by the proteasome. Biochim Biophys Acta. 1823 (2), 524-533, (2012).
Alvarez-Castelao, B. & Castano, J. G. Synphilin-1 inhibits alpha-synuclein degradation by the proteasome. Cell Mol Life Sci. 68 (15), 2643-2654, (2011).
Kong, X., Alvarez-Castelao, B., Lin, Z., Castano, J. G. & Caro, J. Constitutive/hypoxic degradation of HIF-alpha proteins by the proteasome is independent of von Hippel Lindau protein ubiquitylation and the transactivation activity of the protein. J Biol Chem. 282 (21), 15498-15505, (2007).
Diaz-Hernandez, M. et al. Inhibition of 26S proteasome activity by huntingtin filaments but not inclusion bodies isolated from mouse and human brain. J Neurochem. 98 (5), 1585-1596, (2006).
Jimenez, J., Castelao, B. A., Gonzalez-Novo, A. & Sanchez-Perez, M. The role of MEN (mitosis exit network) proteins in the cytokinesis of Saccharomyces cerevisiae. Int Microbiol. 8 (1), 33-42, (2005).
Alvarez-Castelao, B. & Castano, J. G. Mechanism of direct degradation of IkappaBalpha by 20S proteasome. FEBS Lett. 579 (21), 4797-4802, (2005).
Martin-Clemente, B. et al. alpha-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines. J Biol Chem. 279 (51), 52984-52990, (2004).
Location: UCM Veterinary School. Madrid (Spain)
Biochemistry Department
-2 floor
