Abstract：
:X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic disease characterized by the accumulation of very long chain fatty acids (VLCFAs) due to a loss of function of the peroxisomal transporter ABCD1. Here, using in vivo and in vitro models, we demonstrate that autophagic flux was impaired due to elevated mammalian target of rapamycin (mTOR) signaling, which contributed to X-ALD pathogenesis. We also show that excess VLCFAs downregulated autophagy in human fibroblasts. Furthermore, mTOR inhibition by a rapamycin derivative (temsirolimus) restored autophagic flux and inhibited the axonal degenerative process as well as the associated locomotor impairment in the Abcd1 (-) /Abcd2 (-/-) mouse model. This process was mediated through the restoration of proteasome function and redox as well as metabolic homeostasis. These findings provide the first evidence that links impaired autophagy to X-ALD, which may yield a therapy based on autophagy activators for adrenomyeloneuropathy patients.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Launay N,Aguado C,Fourcade S,Ruiz M,Grau L,Riera J,Guilera C,Giròs M,Ferrer I,Knecht E,Pujol Adoi
10.1007/s00401-014-1378-8subject
Has Abstractpub_date
2015-03-01 00:00:00pages
399-415issue
3eissn
0001-6322issn
1432-0533journal_volume
129pub_type
杂志文章abstract：:Vascular smooth muscle cells are involved in deposition of amyloid in brain blood vessels. Accumulation of amyloid-beta peptide (Abeta) in cultured brain vascular smooth muscle cells that overexpress human amyloid-beta precursor protein (APP) Swedish, is strongly enhanced by exposure to iron ions. We studied cellular ...
journal_title：Acta neuropathologica
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doi：10.1007/s00401-009-0497-0
更新日期：2009-05-01 00:00:00
abstract：:Unusual inclusions with some of the features of "reducing bodies" were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhood-onset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appe...
journal_title：Acta neuropathologica
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doi：10.1007/BF00304641
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abstract：:Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibi...
journal_title：Acta neuropathologica
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doi：10.1007/s00401-015-1521-1
更新日期：2016-02-01 00:00:00
abstract：:Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects children in the subsistence-farming communities of East Africa. We report the neuropathologic findings in five fatal cases (13-18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda. Neuropathologic exami...
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doi：10.1007/s00401-018-1909-9
更新日期：2018-11-01 00:00:00
abstract：:Thirty-one squirrel monkey fetuses were exposed to lead acetate given to the mothers perorally during the last three-fourths or two-thirds of pregnancy. The mean maternal blood lead concentration of the group was 37 micrograms/100 ml and the individual means ranged from 22-82 micrograms/100 ml. Examination of the cent...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687421
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abstract：:Detailed neuropathologic and immunohistologic analysis of a case of serologically and polymerase chain reaction-confirmed human immunodeficiency virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is reported in a 73-year-old North American black woman. In addition to the usual neuropath...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00304136
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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abstract：:Human adenovirus type 12 (Ad 12) was inoculated intraperitoneally, intrapleurally, intramuscularly or subcutaneously into newborn rodents. Tumors developed preferentially in the peritoneal cavities in 93.9% of the hamsters and 82.6% of the mice, but none in rats; in contrast to the high incidence of brain tumors in ra...
journal_title：Acta neuropathologica
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-009-0544-x
更新日期：2010-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/BF00696794
更新日期：1975-10-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-016-1562-0
更新日期：2016-09-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296744
更新日期：1994-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688637
更新日期：1985-01-01 00:00:00
abstract：:A 77-year-old man suffered intermittent hemiconvulsions of unknown etiology on the left side for a period of about 5 weeks. At the autopsy, there was marked neuronal loss, severe proliferation of astrocytes and spongiform changes in the right cerebral cortex. The cerebral white matter showed loosening with astroglial ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687782
更新日期：1988-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00309632
更新日期：1995-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000214
更新日期：2000-11-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691427
更新日期：1986-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687981
更新日期：1986-01-01 00:00:00
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pub_type： 杂志文章
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journal_title：Acta neuropathologica
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00294219
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abstract：:A case of classic medulloblastoma that metastasized, despite the absence of local recurrence, to extraneural sites 7 years after treatment is reported. The metastases were, in contrast to the primary tumor, of large cell type and displayed abortive myogenic and, in one site, also rhabdoid differentiation. The primary ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-005-0986-8
更新日期：2005-05-01 00:00:00
abstract：:Recent studies of genetic abnormalities in pediatric low-grade gliomas (LGGs) have focused on activation of the ERK/MAPK pathway by KIAA1549-BRAF gene fusions in the majority of pilocytic astrocytomas (PAs) and by rare mutations in elements of the pathway across histopathologically diverse LGGs. This study reports tha...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-010-0763-1
更新日期：2010-12-01 00:00:00
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journal_title：Acta neuropathologica
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doi：10.1007/BF00294614
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abstract：:Bundles of paired helical filaments (PHF) accumulate in the pyramidal neurons that degenerate during Alzheimer's disease. This neurofibrillary degeneration is highly correlated with clinical signs of dementia. During the degenerating process, Tau proteins, which are the major antigenic components of PHF, are abnormall...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00308912
更新日期：1990-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/BF00294368
更新日期：1989-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s00401-015-1524-y
更新日期：2016-03-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688332
更新日期：1987-01-01 00:00:00
abstract：:The morphology of toxoplasma and its interaction with the cellular elements of the brain were studied in a patient who dies of extensive cerebral toxoplasmosis superimposed on Hodgkin's disease. The cerebral lesions were devoid of inflammatory cellular response and contained numerous organisms mostly in isolated multi...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690360
更新日期：1978-06-30 00:00:00
abstract：:In this study, we used immunohistochemistry to screen for alpha-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multip...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-008-0398-7
更新日期：2008-09-01 00:00:00
