排序方式: 共有2条查询结果,搜索用时 0 毫秒
1
1.
Ramirez A Heimbach A Gründemann J Stiller B Hampshire D Cid LP Goebel I Mubaidin AF Wriekat AL Roeper J Al-Din A Hillmer AM Karsak M Liss B Woods CG Behrens MI Kubisch C 《Nature genetics》2006,38(10):1184-1191
Neurodegenerative disorders such as Parkinson and Alzheimer disease cause motor and cognitive dysfunction and belong to a heterogeneous group of common and disabling disorders. Although the complex molecular pathophysiology of neurodegeneration is largely unknown, major advances have been achieved by elucidating the genetic defects underlying mendelian forms of these diseases. This has led to the discovery of common pathophysiological pathways such as enhanced oxidative stress, protein misfolding and aggregation and dysfunction of the ubiquitin-proteasome system. Here, we describe loss-of-function mutations in a previously uncharacterized, predominantly neuronal P-type ATPase gene, ATP13A2, underlying an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia (PARK9, Kufor-Rakeb syndrome). Whereas the wild-type protein was located in the lysosome of transiently transfected cells, the unstable truncated mutants were retained in the endoplasmic reticulum and degraded by the proteasome. Our findings link a class of proteins with unknown function and substrate specificity to the protein networks implicated in neurodegeneration and parkinsonism. 相似文献
2.
Morgan NV Westaway SK Morton JE Gregory A Gissen P Sonek S Cangul H Coryell J Canham N Nardocci N Zorzi G Pasha S Rodriguez D Desguerre I Mubaidin A Bertini E Trembath RC Simonati A Schanen C Johnson CA Levinson B Woods CG Wilmot B Kramer P Gitschier J Maher ER Hayflick SJ 《Nature genetics》2006,38(7):752-754
Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis. 相似文献
1