The childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) disease caused by AGTPBP1 gene mutations: the Purkinje cell degeneration mouse as an animal model for the study of this human disease
| Autor: | Eugenio Santos, Fernando C. Baltanás, Maria T. Berciano, Miguel Lafarga |
|---|---|
| Přispěvatelé: | Universidad de Cantabria, Instituto de Salud Carlos III, Instituto de Investigación Marqués de Valdecilla, Junta de Castilla y León, Universidad de Salamanca, Fundación Memoria de D. Samuel Solorzano Barruso, Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica, Fondo Europeo de Desarrollo Regional. Universidad de Salamanca SA264P18-UIC076, Instituto de Salud Carlos III (CIBERNED) CB/05/0037, Instituto de Salud Carlos III (CIBERONC) CB16/12/00352, Gobierno regional de Castilla y León, Fundación Samuel-Solorzano Barruso. Universidad de Salamanca FS/32-2020, Instituto de Investigación Valdecilla |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Ataxia
QH301-705.5 Purkinje cell Medicine (miscellaneous) Review Gene mutation pcd General Biochemistry Genetics and Molecular Biology medicine Cognitive decline Biology (General) Neurodegeneration CONDCA Cerebellar ataxia business.industry neurodegeneration medicine.disease AGTPBP1 Pcd Hypotonia NNA1 medicine.anatomical_structure Cerebellar atrophy medicine.symptom CCP1 business Neuroscience |
| Zdroj: | Biomedicines 2021, 9(9), 1157 Biomedicines Biomedicines, Vol 9, Iss 1157, p 1157 (2021) UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) |
| Popis: | © 2021 by the authors. Recent reports have identified rare, biallelic damaging variants of the AGTPBP1 gene that cause a novel and documented human disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), linking loss of function of the AGTPBP1 protein to human neurodegenerative diseases. CONDCA patients exhibit progressive cognitive decline, ataxia, hypotonia or muscle weakness among other clinical features that may be fatal. Loss of AGTPBP1 in humans recapitulates the neurodegenerative course reported in a well-characterised murine animal model harbouring loss-of-function mutations in the AGTPBP1 gene. In particular, in the Purkinje cell degeneration (pcd) mouse model, mutations in AGTPBP1 lead to early cerebellar ataxia, which correlates with the massive loss of cerebellar Purkinje cells. In addition, neurodegeneration in the olfactory bulb, retina, thalamus and spinal cord were also reported. In addition to neurodegeneration, pcd mice show behavioural deficits such as cognitive decline. Here, we provide an overview of what is currently known about the structure and functional role of AGTPBP1 and discuss the various alterations in AGTPBP1 that cause neurodegeneration in the pcd mutant mouse and humans with CONDCA. The sequence of neuropathological events that occur in pcd mice and the mechanisms governing these neurodegenerative processes are also reported. Finally, we describe the therapeutic strategies that were applied in pcd mice and focus on the potential usefulness of pcd mice as a promising model for the development of new therapeutic strategies for clinical trials in humans, which may offer potential beneficial options for patients with AGTPBP1 mutation-related CONDCA. This work was supported by funding received by the Institute of Health Carlos III (CIBERONC, CB16/12/00352 and CIBERNED, CB/05/0037), the Valdecilla Research Institute (IDIVAL, Santander Spain), the Regional Government of Castile and Leon, funds received by the European Regional Development Fund (SA264P18-UIC076; University of Salamanca, Spain) and the Samuel-Solórzano Barruso Foundation (FS/32-2020, University of Salamanca, Spain) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|