Glial filaments are a major brain fraction in infantile neuronal ceroid-lipofuscinosis

Paetau, Anders; Elovaara, Irina; Paasivuo, R; Virtanen, Ismo; Palo, J.; Haltia, Matti

doi:10.1007/bf00686997

Cited by 33 publications

(19 citation statements)

References 33 publications

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“…This well may have also occurred in the analysis of the Tibetian terrier model [22]. Indeed, it has been previously reported that GFAP constitutes a major fraction of the insoluble material in INCL brain autopsy specimens that initially cosediments with autofluorescent storage material but can be separated from this by further manipulations [40]. It is worth noting that vimentin, another intermediate filament protein, was also elevated in the storage body sample from the LINCL mouse, and this may represent the same phenomenon.…”

Section: Discussionmentioning

confidence: 86%

Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material

Xu¹,

Sleat²,

Jadot

et al. 2010

Biochemical Journal

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Classical late neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease of children caused by mutations in TPP1, the gene encoding the lysosomal protease tripeptidyl peptidase 1. LINCL is characterized by lysosomal accumulation of storage material of which only a single protein component, subunit c of mitochondrial ATP synthase, has been well established to date. Identification of other protein constituents of the storage material could provide useful insights into the pathophysiology of disease and the natural substrates for TPP1. We have therefore initiated a proteomic analysis of storage material in brain from a LINCL mouse model. One protein, glial fibrillary acidic protein (GFAP), was found to be elevated in the LINCL mice compared to normal controls in both isolated storage bodies and a lysosome-enriched subcellular fraction that contains storage material. To determine whether GFAP accumulates within the lysosome in LINCL, we examined its intracellular distribution using subcellular fractionation and morphological methods. These experiments demonstrate that GFAP is not a component of the storage material in LINCL, suggesting that reports of GFAP storage in other NCLs may need to be reexamined. A number of other proteins were elevated in the storage material and/or lysosome-enriched fraction from the LINCL mice but it remains unclear whether these proteins are true constituents of the storage material or, like GFAP, if they associate with this material upon purification.

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Section: Discussionmentioning

confidence: 86%

Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material

Xu¹,

Sleat²,

Jadot

et al. 2010

Biochemical Journal

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“…Highly elevated amounts of GFAP in INCL brain has been reported before [27], and may have caused the contamination of storage bodies with a small amount of this protein.…”

Section: Proteins In the Storage Materialsmentioning

confidence: 88%

Storage of saposins A and D in infantile neuronal ceroid‐lipofuscinosis

et al. 1993

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We have isolated storage cytosomes from brain tissue of patients with infantile neuronal ceroid‐lipofuscinosis. The purified storage bodies were subjected to compositional analysis which revealed a high content of proteins, accounting for 43% of dry weight. Saposins A and D, also known as sphingolipid activator proteins (SAPs), were shown to constitute a major portion of the accumulated protein using gel electrophoresis and sequence analysis. This is the first time that saposins have been found to be stored in any form of neuronal ceroid‐lipofuscinosis.

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“…In addition, quantities of ADAM12 mRNA were 18-fold higher in low grade tumors compared with high-grade tumors [70]. These authors also report that overexpression of ADAM12 did not co-localize with glial fibrillary acidic protein (GFAP), an intermediate filament protein expressed by various cell types of the central nervous system, and which is associated with CNS injury and formation of glial scars [71]. This selectivity suggests that ADAM12 may be a useful biomarker for identifying oligodendroglial cell subpopulations in mixed brain tumors [70].…”

Section: : Adam12mentioning

confidence: 99%

A disintegrin and metalloproteinase-12 (ADAM12): Function, roles in disease progression, and clinical implications

Nyren‐Erickson

Jones

Srivastava

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background A disintegrin and metalloproteinase-12 (ADAM12) is a member of the greater ADAM family of enzymes: these are multifunctional, generally membrane-bound, zinc proteases for which there are forty genes known (21 of these appearing in humans). ADAM12 has been implicated in the pathogenesis of various cancers, liver fibrogenesis, hypertension, and asthma, and its elevation or decrease in human serum has been linked to these and other physiological/pathological conditions. Scope In this review, we begin with a brief overview of the ADAM family of enzymes and protein structure. We then discuss the role of ADAM12 in the progression and/or diagnosis of various disease conditions, and we will conclude with an exploration of currently known natural and synthetic inhibitors. Major Conclusions ADAM12 has potential to emerge as a successful drug target, although targeting the metalloproteinase domain with any specificity will be difficult to achieve due to structural similarity between the members of the ADAM and MMP family of enzymes. Overall, more research is required to establish ADAM12 being as a highly desirable biomarker and drug target of different diseases, and their selective inhibitors as potential therapeutic agents. General Significance Given the appearance of elevated levels of ADAM12 in various diseases, particularly breast cancer, our understanding of this enzyme both as a biomarker and a potential drug target could help make significant inroads into both early diagnosis and treatment of disease.

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Glial filaments are a major brain fraction in infantile neuronal ceroid-lipofuscinosis

Cited by 33 publications

References 33 publications

Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material

Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material

Storage of saposins A and D in infantile neuronal ceroid‐lipofuscinosis

A disintegrin and metalloproteinase-12 (ADAM12): Function, roles in disease progression, and clinical implications

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