Abstract：
:Gangliosides have been shown to be necessary for beta-amyloid (Abeta) binding and aggregation. GD3 synthase (GD3S) is responsible for biosynthesis of the b- and c-series gangliosides, including two of the four major brain gangliosides. We examined Abeta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3S (St8sia1), and in a double-transgenic (APP/PSEN1) mouse model of Alzheimer's disease cross-bred with GD3S-/- mice. In primary neurons and astrocytes lacking GD3S, Abeta-induced cell death and Abeta aggregation were inhibited. Like GD3S-/- and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3S-/- "triple-mutant" mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3S-/- triple-mutant mice performed as well as wild-type control and GD3S-/- mice. Consistent with the behavioral improvements, both aggregated and unaggregated Abeta and associated neuropathology were almost completely eliminated in triple-mutant mice. These results suggest that GD3 synthase may be a novel therapeutic target to combat the cognitive deficits, amyloid plaque formation, and neurodegeneration that afflict Alzheimer's patients.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Bernardo A,Harrison FE,McCord M,Zhao J,Bruchey A,Davies SS,Jackson Roberts L 2nd,Mathews PM,Matsuoka Y,Ariga T,Yu RK,Thompson R,McDonald MPdoi
10.1016/j.neurobiolaging.2007.12.022subject
Has Abstractpub_date
2009-11-01 00:00:00pages
1777-91issue
11eissn
0197-4580issn
1558-1497pii
S0197-4580(07)00498-8journal_volume
30pub_type
杂志文章abstract：:Mutations in the OPTN gene are well known to be associated with the development of glaucoma. Recently, unique variations in the same gene have been reported in familial and sporadic Japanese cases of amyotrophic lateral sclerosis (ALS). We set out to evaluate the frequency of OPTN mutations in a sample of our familial...
journal_title：Neurobiology of aging
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abstract：:This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 ...
journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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abstract：:Frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17) are hereditary tauopathies affecting at least 50 known kindred worldwide. Most kindred present with severe behavioral or psychiatric manifestations progressing to dementia, while some kindred first manifest a parkinsonian-plus syndrome. Nine ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
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更新日期：2001-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2009-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：1989-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
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更新日期：2018-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.02.006
更新日期：2012-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00121-4
更新日期：2000-03-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.01.017
更新日期：2013-07-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2012-02-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/s0197-4580(03)00057-5
更新日期：2003-05-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
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更新日期：1994-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2011.09.006
更新日期：2011-12-01 00:00:00
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journal_title：Neurobiology of aging
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2008-06-01 00:00:00
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journal_title：Neurobiology of aging
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更新日期：2019-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2004-08-01 00:00:00
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journal_title：Neurobiology of aging
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更新日期：2018-01-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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journal_title：Neurobiology of aging
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更新日期：1994-11-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2012-05-01 00:00:00
abstract：:Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding var...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2019-06-01 00:00:00
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journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.01.012
更新日期：2014-07-01 00:00:00
abstract：:The complement system has been shown to have a critical pathogenetic role in amyotrophic lateral sclerosis (ALS). Recently a C7 variant in rs3792646 was linked to neurodegenerative diseases in a Chinese population. We used whole exome sequencing to evaluate the role of C7 (rs3792646) in ALS in a Chinese cohort with 19...
journal_title：Neurobiology of aging
pub_type： 杂志文章
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更新日期：2020-11-13 00:00:00
