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The aging of the population poses a growing burden in society. This is associated with an increase in disability and diseases that have a high impact on health care, on patients and their families. Also, aging is associated with the emergence of different neurodegenerative diseases among which include Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Therefore, the development of advanced biological markers, new drugs and appropriate technology is the key to establishing a treatment for these diseases, which is currently an important social challenge. In our laboratory we study the molecular basis of neurodegeneration. The research projects we develop have a multidisciplinary approach that combines basic and translational research, using cell culture techniques, murine models and postmortem samples from patients with AD, PD and ALS.

Currently, our research is focused on addressing three key aspects of neurodegeneration:

1) Proteinopathy: the accumulation of beta-amyloid plaques and neurofibrillary tangles of TAU protein, involved in neurodegeneration processes, appear in AD. In the case of PD, the alpha-synuclein protein plays a key role in the degeneration of dopaminergic neurons, forming part of the Lewy bodies. And in ALS there is alteration of RNA metabolism and homeostasis. Recent work that connects TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves the aggregation of proteins as part of their normal function, is altered in ALS. We are interested in determining the role of these proteins in the neurodegeration process.

2) Inflammation: it is a process that appears in the first stages of the disease and aggravates neurodegeneration. Alzheimer's and Parkinson's diseases are characterized by what is called chronic low-grade inflammation, so we want to determine what causes this inflammation and how it can be prevented or stopped.

3) Oxidative stress: it is imbalance between the production of reactive oxygen species and the ability of a biological system to quickly decode the intermediate reagents or repair the resulting damage. It has been observed that this imbalance is present in these neurodegenerative diseases, so we want to study what it is that causes it and how to reverse it.

RECENT PUBLICATIONS

4: Galán-Ganga M, Rodríguez-Cueto C, Merchán-Rubira J, Hernández F, Ávila J, Posada-Ayala M, Lanciego JL, Luengo E, Lopez MG, Rábano A, Fernández-Ruiz J, Lastres-Becker I. Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration. Acta Neuropathol Commun. 2021 May 17;9(1):90. doi: 10.1186/s40478-021-01196-5. PMID: 34001284; PMCID: PMC8130522.

5: Lastres-Becker I, Porras G, Arribas-Blázquez M, Maestro I, Borrego-Hernández D, Boya P, Cerdán S, García-Redondo A, Martínez A, Martin-Requero Á. Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy. Int J Mol Sci. 2021 Mar 16;22(6):3007. doi: 10.3390/ijms22063007. PMID: 33809456; PMCID: PMC8000750.

6: Klionsky DJ,...Lastres-Becker I, Tong CK. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8. PMID: 33634751; PMCID: PMC7996087.

7: Lastres-Becker I. Special Issue "Role of NRF2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches". Biomolecules. 2021 Feb 2;11(2):202. doi: 10.3390/biom11020202. PMID: 33540503; PMCID: PMC7912791.

8: Castro-Sánchez S, Zaldivar-Diez J, Luengo E, López M.G, Gil C, Martínez A, Lastres-Becker I. Cognitive enhancement, TAU phosphorylation reduction, and neuronal protection by the treatment of a LRRK2 inhibitor in a tauopathy mouse model. Neurobiology of Aging. 2020

9: Martin-Hurtado A, Lastres-Becker I, Cuadrado A, Garcia-Gonzalo FR. NRF2 and Primary Cilia: An Emerging Partnership. Antioxidants (Basel). 2020;9(6):475. Published 2020 Jun 2. doi:10.3390/antiox9060475.

10: Martin-Hurtado A, Martin-Morales R, Robledinos-Antón N, Blanco R, Palacios-Blanco I, Lastres-Becker I, Cuadrado A, Garcia-Gonzalo FR. NRF2-dependent gene expression promotes ciliogenesis and Hedgehog signaling. Sci Rep. 2019 Sep 25;9(1):13896. doi: 10.1038/s41598-019-50356-0.

11: Lastres-Becker I., Nonis FD., Nowock J., Auburger G. NEW ALTERNATIVE SPLICING VARIANTS OF THE SCA2 TRANSCRIPT. Neurological Research and Practice. 2019.

12: Galán-Ganga M, Del Río R, Jiménez-Moreno N, Díaz-Guerra M, Lastres-Becker I. Cannabinoid CB2 Receptor Modulation by the Transcription Factor NRF2 is Specific in Microglial Cells. Cell Mol Neurobiol. 2019 Aug 5. doi: 10.1007/s10571-019-00719-y. [Epub ahead of print].

FUNDINGS

Our laboratory receives funding from various national and international sources, including:

1: “Modulación del receptor cannabinoide CB2 como nueva estrategia terapéutica para proteger contra la neurodegeneración inducida por TAU” Fundación Tatiana Pérez de Guzmán El Bueno. PI: Isabel Lastres-Becker. Febrero 2021-Enero 2024.

2: Análisis del transporte de gránulos de RNA y traducción de proteínas in situ en ELA: ¿implicación de SATUFEN y TDP-43? FundELA. PI: Isabel Lastres-Becker. 30.000. Noviembre 2019-Agosto 2021.

3: Convocatoria 2019 - «Proyectos de I+D+i» Ministerio de Ciencia, Innovación y Universidades: “AGING AND NEURODEGENERATION TARGETING BY PROTEIN KINASE SMALL MOLECULES INHIBITORS” . IP: Isabel Lastres-Becker/ Ana Martínez

4: Fundación Tatiana Pérez de Guzmán el Bueno(2019-2021) "Alteraciones de la mitofagia en la enfermedad de Parkinson". PI: Patricia Boya. Co-investigator: Isabel Lastres-Becker.

5: Diseño y desarrollo de fármacos innovadores para el tratamiento de la esclerosis lateral amiotrófica” . Conserjería de educación e investigación de la Comunidad de Madrid B2017/BMD-3813 ELA-Madrid (2018-2021). PI: Ana Martínez/Isabel Lastres-Becker

6: Papel de NRF2 en la función y el destino del cerebro con Alzheimer . This work is supported by Spanish Ministerio de Ciencia e Innovacion Grant SAF2016-76520-R (2017-2020). PI: Antonio Cuadrado/Isabel Lastres-Becker.

7: Targeting NRF2 with BG-12 to modify Parkinson's disease progression in the AAV6-alpha-synuclein mouse model founded by Biogen Iberica (2013-2015). PI: Antonio Cuadrado. Co-investigator: Isabel Lastres-Becker.

8: Health Research Foundation 2000 in neurodegenerative diseases (2013) for the project: Characterization of the proteasome and autophagy degradation system in an AAV6-a-synuclein model of Parkinson's disease: involvement of the transcription factor Nrf2” (2013-2014). PI: Isabel Lastres-Becker.

AWARDS

2021: Premio a la publicación más citada publicada hace 5 años del IdiPAZ

2020: Premio a la publicación más relevante en el área de Neurociencias del IdiPaz

2019: Premio a la publicación más citada publicada hace 5 años del IdiPAZ

2019: Premio especial Arquímedes del Jurado, al trabajo de Fin de Máster del estudiante Marcos Galán Ganga.

2018: Premio I Congreso Internacional de la Comunidad de ELA al mejor póster en la categoría de INVESTIGACIÓN.

2015: Premio a la publicación más relevante del Área 1-Neurociencias del IdiPaz

2012: Premio a la publicación más relevante del Área 1-Neurociencias del IdiPaz

2012: Premio a la major presentación oral en el 6th European Congress of Pharmacology.

2010: Bolsa de Investigación L'Oreal-Unesco para mujeres en la Ciencia.