Cellular models of Batten disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Review

Minnis, Christopher J.^1,3  Thornton, Christopher D.²  FitzPatrick, Lorna M.²  McKay, Tristan R.² 

[1] UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England

[2] Manchester Metropolitan Univ, Ctr Biosci, Manchester M1 5GD, Lancs, England

[3] Royal Vet Coll, Dept Comparat Biomed Sci, Royal Coll St, London NW1 0TU, England

关键词: Yeast;    Batten disease;    NCL;    Ceroid;    Cellular models;    Neurodegeneration;   

DOI  :  10.1016/j.bbadis.2019.165559

来源: Elsevier

【 摘 要 】

The Neuronal Ceroid Lipofuscinoses (NCL), otherwise known as Batten disease, are a group of neurodegenerative diseases caused by mutations in 13 known genes. All except one NCL is autosomal recessive in inheritance, with similar aetiology and characterised by the accumulation of autofluorescent storage material in the lysosomes of cells. Age of onset and the rate of progression vary between the NCLs. They are collectively one of the most common lysosomal storage diseases, but the enigma remains of how genetically distinct diseases result in such remarkably similar pathogenesis. Much has been learnt from cellular studies about the function of the proteins encoded by the affected genes. Such research has utilised primitive unicellular models such as yeast and amoeba containing gene orthologues, cells derived from naturally occurring (sheep) and genetically engineered (mouse) animal models or patient-derived cells. Most recently, patient-derived induced pluripotent stem cell (iPSC) lines have been differentiated into neural cell-types to study molecular pathogenesis in the cells most profoundly affected by disease. Here, we review how cell models have informed much of the biochemical understanding of the NCLs and how more complex models are being used to further this understanding and potentially act as platforms for therapeutic efficacy studies in the future.

【 授权许可】

Free