Cell biology and function of neuronal ceroid lipofuscinosis-related proteins

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1832

Review

Kollmann, Katrin¹  Uusi-Rauva, Kristiina^2,3  Scifo, Enzo^4,5  Tyynela, Jaana⁶  Jalanko, Anu³  Braulke, Thomas¹ 

[1] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Dept Biochem, D-20246 Hamburg, Germany

[2] Folkhalsan Inst Genet, Helsinki, Finland

[3] Biomedicum Helsinki, Natl Inst Hlth & Welf, Publ Hlth Genom, Helsinki, Finland

[4] Univ Helsinki, Inst Biomed, Meilahti Clin Prote Core Facil, Helsinki, Finland

[5] Finnish Grad Sch Neurosci, Helsinki, Finland

[6] Univ Helsinki, Inst Biomed Biochem & Dev Biol, Helsinki, Finland

关键词: Lysosome;    Neurodegeneration;    Lysosomai storage disorder;    Mannose 6-phosphate;    CSP alpha;    Progranulin;   

DOI  :  10.1016/j.bbadis.2013.01.019

来源: Elsevier

【 摘 要 】

Neuronal ceroid lipofuscinoses (NCL) comprise a group of inherited lysosomal disorders with variable age of onset, characterized by lysosomal accumulation of autofluorescent ceroid lipopigments, neuroinflammation, photoreceptor- and neurodegeneration. Most of the NCL-related genes encode soluble and transmembrane proteins which localize to the endoplasmic reticulum or to the endosomal/lysosomal compartment and directly or indirectly regulate lysosomal function. Recently, exome sequencing led to the identification of four novel gene defects in NCL patients and a new NCL nomenclature currently comprising CLN1 through CLN14. Although the precise function of most of the NCL proteins remains elusive, comprehensive analyses of model organisms, particularly mouse models, provided new insight into pathogenic mechanisms of NCL diseases and roles of mutant NCL proteins in cellular/subcellular protein and lipid homeostasis, as well as their adaptive/compensatorial regulation at the transcriptional level. This review summarizes the current knowledge on the expression, function and regulation of NCL proteins and their impact on lysosomal integrity. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

Free