Abstract
The NCLs (neuronal ceroid lipofuscinosis) are forms of neurodegenerative disease that affect people of all ages and ethnicities but are most prevalent in children. Commonly known as Batten disease, this debilitating neurological disorder is comprised of 13 different subtypes that are categorized based on the particular gene that is mutated (CLN1-8, CLN10-14). The pathological mechanisms underlying the NCLs are not well understood due to our poor understanding of the functions of NCL proteins. Only one specific treatment (enzyme replacement therapy) is approved, which is for the treating the brain in CLN2 disease. Hence there remains a desperate need for further research into disease-modifying treatments. In this review, we present and evaluate the genes, proteins and studies performed in the social amoeba, nematode, fruit fly, zebrafish, mouse and large animals pertinent to NCL. In particular, we highlight the use of multicellular model organisms to study NCL protein function, pathology and pathomechanisms. Their use in testing novel therapeutic approaches is also presented. With this information, we highlight how future research in these systems may be able to provide new insight into NCL protein functions in human cells and aid in the development of new therapies.
Highlights
Neuronal Ceroid Lipofuscinosis is a group of fatal neurodegenerative diseases that are characterised by lysosomal storage of ceroid lipofuscin
Concluding remarks This review presents an update on the range of multicellular model organisms and disease models being used for Neuronal Ceroid Lipofuscinosis (NCL) research, in the hope that this will stimulate researchers to collaborate and employ the most suitable model(s) for their study
This is important before a therapeutic enters clinical trial, where positive outcomes from studies using more than one organism will reduce the risk of failure
Summary
Neuronal Ceroid Lipofuscinosis is a group of fatal neurodegenerative diseases that are characterised by lysosomal storage of ceroid lipofuscin. Once a set of compounds has been identified, animals are used to verify which compounds improve the disease in the animal and, many compounds fail at this point Of those compounds that do show improvement in the animal model, several will fail at clinical trial because the result (efficacy or toxicity) in the animal was not representative of humans [8]. A further issue is that it is difficult to identify the target of the lead compound This is often required before approval of a new drug is granted but can be waived for rare diseases where a treatment is not yet available. Another route to treatment is the replacement of a protein known to be missing, for example by gene therapy or enzyme replacement therapy. In the final section (Section 16), we provide concluding remarks on the future of NCL research using model systems
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