Abstract
The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. The social amoeba Dictyostelium discoideum has proven to be an exceptional model organism for studying a wide range of neurological disorders, including the NCLs. The Dictyostelium genome contains homologs of 11 of the 13 NCL genes. Its life cycle, comprised of both single-cell and multicellular phases, provides an excellent system for studying the effects of NCL gene deficiency on conserved cellular and developmental processes. In this review, we highlight recent advances in NCL research using Dictyostelium as a biomedical model.
Highlights
The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages
Mutations in any one of 13 genetically distinct genes can cause Batten disease (CLN1-8, CLN10-14) [1]. These genes encode lysosomal enzymes (PPT1/CLN1, tripeptidyl peptidase 1 (TPP1)/CLN2, CLN5, cathepsin D (CTSD)/CLN10, CTSF/CLN13), proteins that peripherally associate with membranes (DNAJC5/CLN4, KCTD7/CLN14), proteins that are present in the secretory pathway (CLN5, PGRN/CLN11), and several transmembrane domain-containing proteins (CLN3, CLN6, MFSD8/CLN7, CLN8, ATP13A2/CLN12) [4]
The 24-h life cycle of Dictyostelium is comprised of distinct single-cell and multicellular phases, which allows for the study of conserved cellular and developmental processes [9]
Summary
The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are forms of neurodegeneration that affect people of all ages and ethnic backgrounds [1]. The ability to knockout genes using homologous recombination or CRISPR/Cas9-mediated targeting has made Dictyostelium a powerful model system for studying the functions of proteins linked to human disease [10,11]. Spores growth are dispersed and germinate when nutrients metazoan cells, Dictyostelium and development relies on fundamental processes become available, restarting the life cycle. Work in Dictyostelium has made valuable contributions to our Dictyostelium has proven to be an exceptional organism for studying the cellular and molecular understanding of the functions of proteins linked to human neurological disorders, including mechanisms underlying Batten disease [7]. Dictyostelium has proven to be an exceptional organism for studying the Recent work on Dictyostelium has provided fresh new insight into the functions of TPP1/CLN2, CLN3, cellular and molecular mechanisms underlying Batten disease [7]. UsingofDictyostelium to Study how these new findings have enhanced our knowledge of NCL protein function in humans
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
