Biochimica et biophysica acta
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Biochim. Biophys. Acta · Dec 2013
Comparative StudyAnoctamin 1 dysregulation alters bronchial epithelial repair in cystic fibrosis.
Cystic fibrosis (CF) airway epithelium is constantly subjected to injury events due to chronic infection and inflammation. Moreover, abnormalities in CF airway epithelium repair have been described and contribute to the lung function decline seen in CF patients. In the last past years, it has been proposed that anoctamin 1 (ANO1), a Ca(2+)-activated Cl(-) channel, might offset the CFTR deficiency but this protein has not been characterized in CF airways. ⋯ In all these models, ANO1 expression was markedly lower in CF compared to non-CF. Finally, we established that ANO1 inhibition or overexpression was associated respectively with decreases and increases in cell proliferation and migration. In summary, our study demonstrates involvement of ANO1 decreased activity and expression in abnormal CF airway epithelial repair and suggests that ANO1 correction may improve this process.
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Biochim. Biophys. Acta · Nov 2013
ReviewGenetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses.
The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders that mainly affect children and are grouped together by similar clinical features and the accumulation of autofluorescent storage material. More than a dozen genes containing nearly 400 mutations underlying human NCLs have been identified. ⋯ There are still disease subgroups with unknown molecular genetic backgrounds. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
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Biochim. Biophys. Acta · Nov 2013
ReviewPathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease).
The neuronal ceroid lipofuscinoses (NCL, Batten disease) are a group of inherited neurodegenerative diseases. Infantile neuronal ceroid lipofuscinosis (INCL, infantile Batten disease, or infantile CLN1 disease) is caused by a deficiency in the soluble lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1) and has the earliest onset and fastest progression of all the NCLs. Several therapeutic strategies including enzyme replacement, gene therapy, stem cell-mediated therapy, and small molecule drugs have resulted in minimal to modest improvements in the murine model of PPT1-deficiency. ⋯ Different therapeutic targets will need to be identified and novel strategies developed in order to effectively treat forms of NCL caused by deficiencies in integral membrane proteins such as juvenile neuronal ceroid lipofuscinosis. Finally, the challenge with all of the NCLs will lie in early diagnosis, improving the efficacy of the treatments, and effectively translating them into the clinic. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
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Biochim. Biophys. Acta · Nov 2013
ReviewUse of model organisms for the study of neuronal ceroid lipofuscinosis.
Neuronal ceroid lipofuscinoses are a group of fatal progressive neurodegenerative diseases predominantly affecting children. Identification of mutations that cause neuronal ceroid lipofuscinosis, and subsequent functional and pathological studies of the affected genes, underpins efforts to investigate disease mechanisms and identify and test potential therapeutic strategies. ⋯ In this review, we will discuss the ethical issues associated with experiments using model organisms, the factors underlying the choice of model organism, the disease models and genetic tools available, and the contributions of those disease models and tools to neuronal ceroid lipofuscinosis research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
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Biochim. Biophys. Acta · Nov 2013
ReviewBioinformatic perspectives in the neuronal ceroid lipofuscinoses.
The neuronal ceroid lipofuscinoses (NCLs) are a group of rare genetic diseases characterised clinically by the progressive deterioration of mental, motor and visual functions and histopathologically by the intracellular accumulation of autofluorescent lipopigment - ceroid - in affected tissues. The NCLs are clinically and genetically heterogeneous and more than 14 genetically distinct NCL subtypes have been described to date (CLN1-CLN14) (Haltia and Goebel, 2012 [1]). In this review we will chronologically summarise work which has led over the years to identification of NCL genes, and outline the potential of novel genomic techniques and related bioinformatic approaches for further genetic dissection and diagnosis of NCLs. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.