Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis
- PMID: 21118112
- DOI: 10.1042/BST0381484
Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis
Abstract
The NCLs (neuronal ceroid lipofuscinoses) are the most common inherited paediatric neurodegenerative disorder. Although genetically distinct, NCLs can be broadly divided into two categories: one in which the mutation results in a defect in a transmembrane protein, and the other where the defect lies in a soluble lysosomal enzyme. A number of therapeutic approaches are applicable to the soluble lysosomal forms of NCL based on the phenomenon of cross-correction, whereby the ubiquitously expressed mannose 6-phosphate/IGF (insulin-like growth factor) II receptor provides an avenue for endocytosis, trafficking and lysosomal processing of extracellularly delivered enzyme. The present review discusses therapeutic utilization of cross-correction by enzyme-replacement therapy, gene therapy and stem cell therapy for the NCLs, along with an overview of the recent progress in translating these treatments into the clinic.
Similar articles
-
Human palmitoyl protein thioesterase: evidence for lysosomal targeting of the enzyme and disturbed cellular routing in infantile neuronal ceroid lipofuscinosis.EMBO J. 1996 Oct 1;15(19):5240-5. EMBO J. 1996. PMID: 8895569 Free PMC article.
-
Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5.Hum Mutat. 1999;14(3):199-215. doi: 10.1002/(SICI)1098-1004(1999)14:33.0.CO;2-A. Hum Mutat. 1999. PMID: 10477428 Review.
-
Neuronal ceroid lipofuscinoses therapeutic strategies: past, present and future.Biochim Biophys Acta. 2006 Oct;1762(10):945-53. doi: 10.1016/j.bbadis.2006.08.004. Epub 2006 Aug 16. Biochim Biophys Acta. 2006. PMID: 17049436 Review.
-
The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations.Hum Mutat. 2010 Mar;31(3):356-65. doi: 10.1002/humu.21195. Hum Mutat. 2010. PMID: 20052765
-
Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease).Biochim Biophys Acta. 2013 Nov;1832(11):1906-9. doi: 10.1016/j.bbadis.2013.05.026. Epub 2013 Jun 6. Biochim Biophys Acta. 2013. PMID: 23747979 Free PMC article. Review.
Cited by
-
Progress in the Development of Small Molecule Therapeutics for the Treatment of Neuronal Ceroid Lipofuscinoses (NCLs).J Med Chem. 2016 May 26;59(10):4415-27. doi: 10.1021/acs.jmedchem.5b01020. Epub 2015 Nov 24. J Med Chem. 2016. PMID: 26565590 Free PMC article. Review.
-
Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study.Lancet Neurol. 2014 Aug;13(8):777-87. doi: 10.1016/S1474-4422(14)70142-5. Epub 2014 Jul 2. Lancet Neurol. 2014. PMID: 24997880 Free PMC article. Clinical Trial.
-
An iPSC-Derived Neuron Model of CLN3 Disease Facilitates Small Molecule Phenotypic Screening.ACS Pharmacol Transl Sci. 2020 Sep 1;3(5):931-947. doi: 10.1021/acsptsci.0c00077. eCollection 2020 Oct 9. ACS Pharmacol Transl Sci. 2020. PMID: 33073192 Free PMC article.
-
Defining and designing polymers and hydrogels for neural tissue engineering.Neurosci Res. 2012 Mar;72(3):199-213. doi: 10.1016/j.neures.2011.12.005. Epub 2011 Dec 17. Neurosci Res. 2012. PMID: 22192467 Free PMC article. Review.
-
Neuroprotection and lifespan extension in Ppt1(-/-) mice by NtBuHA: therapeutic implications for INCL.Nat Neurosci. 2013 Nov;16(11):1608-17. doi: 10.1038/nn.3526. Epub 2013 Sep 22. Nat Neurosci. 2013. PMID: 24056696 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous
