Animal models of neurodegeneration

Principal Investigator

Abraham Acevedo Arozena, PhD

Researcher «Miguel Servet type II», SCS/FIISC, Research Unit, HUC

Collaborating researchers (PhDs)

PhD students and researchers in training

  • Ramón A. Muñoz de Bustillo Alfaro (Doctoral Program in Health Sciences ULL, 2021-2025)

Lines of research

Our research focuses on identifying and elucidating novel genetic pathways involved in neurodegeneration, particularly Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD), through the development of new mouse models of these diseases using patient-derived material. These studies are central to a broader collaboration with leading national and international laboratories, incorporating unique expertise in genetics, biochemistry, and cell biology. The group's work centers on developing novel mouse models of ALS/FTD, with a particular focus on the biology of TDP-43, the key pathological protein involved in ALS. Building on these approaches, we are establishing a broad international collaboration that includes several laboratories in Europe, the USA, and Spain. Additionally, we work with most of the ITB groups interested in generating specific mouse models of human diseases, collaborating on the development of a new platform.

Funded projects

  • Studying the central role of the TDP-43 protein in ALS and other TDP-43 proteinopathies (PI20/00422). PI: Abraham Acevedo. Carlos III Health Institute (2021-2023, €123,420)
  • Role of cytoplasmic localization of TDP-43 in the pathogenesis of amyotrophic lateral sclerosis and other TDP-43 proteinopathies (ProID2021010082). PI: Abraham Acevedo. Canary Islands Agency for Research, Innovation and the Information Society, ACIISI (2022-2023, €70,000)

Publications 2023

  • Fisher EMC, Greensmith L, Malaspina A, Fratta P, Hanna MG, Schiavo G, Isaacs AM, Orrell RW, Cunningham TJ, Acevedo Arozena A. Opinion: more mouse models and more translation needed for ALS. Neurotherapeutics. 2023 May 4;18(1):30. doi:10.1186/s13024-023-00619-2

Other representative publications from recent years

  • Devoy A, Price G, De Giorgio F, Bunton-Stasyshyn R, Thompson D, Gasco S, Allan A, Codner GF, Nair RR, Tibbit C, McLeod R, Ali Z, Noda J, Marrero-Gagliardi A, Brito-Armas JM, Öztürk MM, Simon M, O'Neill E, Bryce-Smith S, Harrison J, Atkins G, Corrochano S, Stewart M, Teboul L, Acevedo-Arozena A, Fisher EMC, Cunningham TJ. Generation and analysis of innovative genomically humanized knockin SOD1, TARDBP (TDP-43), and FUS mouse models. iScience. 2021 Nov;24(12):103463. DOI: 10.1016/j.isci.2021.103463
  • Fratta P, Sivakumar P, Humphrey J, Lo K, Ricketts T, Oliveira H, Brito-Armas JM, Kalmar B, Ule A, Yu Y, Birsa N, Bodo C, Collins T, Conicella AE, Mejia Maza A, Marrero-Gagliardi A, Stewart M, Mianne J, Corrochano S, Emmett W, Codner G, Groves M, Fukumura R, Gondo Y, Lythgoe M, Pauws E, Peskett E, Stanier P, Teboul L, Hallegger M, Calvo A, Chiò A, Isaacs AM, Fawzi NL, Wang E, Housman DE, Baralle F, Greensmith L, Buratti E, Plagnol V, Fisher EM, Acevedo-Arozena A. Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis. EMBO Journal. 2018 Jun;37(11). DOI: 10.15252/embj.201798684
  • Corrochano S, Blanco G, Williams D, Wettstein J, Simon M, Kumar S, Moir L, Agnew T, Stewart M, Landman A, Kotiadis VN, Duchen MR, Wackerhage H, Rubinsztein DC, Brown SDM, Acevedo-Arozena A. A genetic modifier suggests that endurance exercise exacerbates Huntington's disease. Hum Mol Genet. 2018 May;27(10):1723-1731. DOI: 10.1093/hmg/ddy077
  • Joyce PI, Fratta P, Landman AS, McGoldrick P, Wackerhage H, Groves M, Busam BS, Galino J, Corrochano S, Beskina OA, Esapa C, Ryder E, Carter S, Stewart M, Codner G, Hilton H, Teboul L, Tucker J, Lionikas A, Estabel J, Ramirez-Solis R, White JK, Brandner S, Plagnol, V, Bennet DL, Abramov AY, Greensmith L, Fisher EM, Acevedo-Arozena A. Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration. Hum Mol Genet. 2016 Jan;25(2):291-307. DOI: 10.1093/hmg/ddv471