دورية أكاديمية
Filipin complex-reactive brain lesions: a cautionary tale.
| العنوان: | Filipin complex-reactive brain lesions: a cautionary tale. |
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| المؤلفون: | Lau AA; Childhood Dementia Research Group, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, 5042, Australia., Trim PJ; Proteomics, Metabolomics and MS-Imaging Core Facility, SAHMRI, Adelaide, South Australia, 5000, Australia., King BM; Childhood Dementia Research Group, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, 5042, Australia., Hassiotis S; Childhood Dementia Research Group, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, 5042, Australia.; Histopathology and Biological Imaging, Future Industries Institute, University of South Australia., Hung YH; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, 3052, Australia., Bush AI; Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, 3052, Australia., Snel MF; Proteomics, Metabolomics and MS-Imaging Core Facility, SAHMRI, Adelaide, South Australia, 5000, Australia., Hemsley KM; Childhood Dementia Research Group, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, 5042, Australia. |
| المصدر: | Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2023 Dec 19, pp. e12950. Date of Electronic Publication: 2023 Dec 19. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 7609829 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2990 (Electronic) Linking ISSN: 03051846 NLM ISO Abbreviation: Neuropathol Appl Neurobiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Blackwell Scientific Publications. |
| مستخلص: | Objective: Filipin complex is an autooxidation-prone fluorescent histochemical stain used in the diagnosis of Niemann-Pick Disease Type C (NP-C), a neurodegenerative lysosomal storage disorder. It is also widely used by researchers examining the distribution and accumulation of unesterified cholesterol in cell and animal models of neurodegenerative diseases including NP-C and Sanfilippo syndrome (mucopolysaccharidosis IIIA; MPS IIIA). Recently, it has been suggested to be useful in studying Alzheimer's and Huntington's disease. Given filipin's susceptibility to photobleaching, we sought to establish a quantitative biochemical method for free cholesterol measurement. Methods: Brain tissue from mice with MPS IIIA was stained with filipin. Total and free cholesterol in brain homogenates was measured using a commercially available kit and a quantitative LC-MS/MS assay was developed. Gangliosides GM1, GM2 and GM3 were also quantified using LC-MS/MS. Results: As anticipated, the MPS IIIA mouse brain displayed large numbers of filipin-positive intra-cytoplasmic inclusions, presumptively endo-lysosomes. Challenging the prevailing dogma, however, we found no difference in the amount of free cholesterol in MPS IIIA mouse brain homogenates cf. control tissue, using either the fluorometric kit or LC-MS/MS assay. Filipin has previously been reported to bind to GM1 ganglioside, however, this lipid does not accumulate in MPS IIIA cells/tissues. Using a fluorometric assay, we demonstrate for the first time that filipin cross-reacts with both GM2 and GM3 gangliosides, explaining the filipin-reactive inclusions observed in MPS IIIA brain cells. Conclusion: Filipin is not specific for free cholesterol, and positive staining in any setting should be interpreted with caution. (This article is protected by copyright. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Filipin complex; Niemann-Pick C; cholesterol; ganglioside; lysosomal; mouse; mucopolysaccharidosis |
| تواريخ الأحداث: | Date Created: 20231219 Latest Revision: 20231219 |
| رمز التحديث: | 20231220 |
| DOI: | 10.1111/nan.12950 |
| PMID: | 38112248 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2990 |
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| DOI: | 10.1111/nan.12950 |