Abstract:
:Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. Expression of Parkin associated endothelin-receptor like receptor (Pael-R) in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre recombinase into the striatum. Upregulation of Pael-R in the substantia nigra pars compacta of mice by retrograde infection induced endoplasmic reticulum (ER) stress leads to death of dopaminergic neurons. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150 (150 kDa oxygen-regulated protein). Dopamine-related toxicity was also a key factor, as a dopamine synthesis inhibitor blocked neuronal death in parkin null mice. These data suggest a model in which ER- and dopamine-related stress are major contributors to decreased viability of dopaminergic neurons in a setting relevant to Parkinson's disease.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Kitao Y,Imai Y,Ozawa K,Kataoka A,Ikeda T,Soda M,Nakimawa K,Kiyama H,Stern DM,Hori O,Wakamatsu K,Ito S,Itohara S,Takahashi R,Ogawa Sdoi
10.1093/hmg/ddl439subject
Has Abstractpub_date
2007-01-01 00:00:00pages
50-60issue
1eissn
0964-6906issn
1460-2083pii
ddl439journal_volume
16pub_type
杂志文章abstract::Current evidence indicates that excess brain cholesterol regulates amyloid-β (Aβ) deposition, which in turn can regulate cholesterol homeostasis. Moreover, Aβ neurotoxicity is potentiated, in part, by mitochondrial glutathione (mGSH) depletion. To better understand the relationship between alterations in cholesterol h...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt201
更新日期:2013-09-01 00:00:00
abstract::We have defined unexpectedly extensive copy number variation at the human anti-microbial alpha-defensin genes DEFA1 and DEFA3, encoding human neutrophil peptides HNP-1, HNP-2 and HNP-3. There was variation in both number and position of DEFA1/DEFA3 genes in arrays of 19 kb tandem repeats on 8p23.1, so that the DEFA1 a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi209
更新日期:2005-07-15 00:00:00
abstract::ABP-280 is a ubiquitous actin binding protein present in the cytoskeleton of many different cell types. ABP-280 was mapped to distal Xq28, 50-60 kb downstream of the Green Colour Pigment (GCP) genes. To establish if ABP-280 may be a candidate for one of the muscle disease localized by linkage analysis to distal Xq28 w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.6.761
更新日期:1993-06-01 00:00:00
abstract::X chromosome inactivation (XCI) is an epigenetic mechanism that silences the majority of genes on one X chromosome in females. Previous studies have suggested that the spread of XCI might be facilitated in part by common repeats such as long interspersed nuclear elements (LINEs). However, owing to the unusual sequence...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt553
更新日期:2014-03-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase ( SOD1 ), which catalyses the dismutation of the superoxide...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.13.2045
更新日期:1998-12-01 00:00:00
abstract::Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularizatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz159
更新日期:2019-10-15 00:00:00
abstract::Degradation of fibrillar collagens is believed to be involved in the rupture of the fetal membranes during normal parturition and when the membranes rupture prematurely. Matrix metalloproteinase 1 (MMP1) is a key enzyme involved in extracellular matrix turnover, and genetic variation in the MMP1 promoter is associated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm381
更新日期:2008-04-15 00:00:00
abstract::Mutations in Fused in sarcoma (FUS) gene cause a subset of familial amyotrophic lateral sclerosis (ALS), a fatal motor neuron degenerative disease. Wild-type FUS is largely localized in the nucleus, but mutant FUS accumulates in the cytoplasm and forms inclusions. It is unclear whether FUS depletion from the nucleus o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv239
更新日期:2015-09-15 00:00:00
abstract::Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltrans...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp110
更新日期:2009-06-01 00:00:00
abstract::Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv336
更新日期:2015-11-01 00:00:00
abstract::Long range restriction site maps of 13 Mb of mouse chromosome 1 and 11 Mb of human chromosome 1 were constructed using a framework provided by a detailed mouse genetic map. Where an unambiguous gene order could be determined in both species (14 genes), the human and mouse orders were identical. In addition, the distan...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/1.8.613
更新日期:1992-11-01 00:00:00
abstract::Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome (KRS) characterized by juvenile-onset parkinsonism, pyramidal signs and dementia. PARK9 belongs to type 5 P-type ATPase with its putative function as a cation transporter. Loss of PARK9 leads to lysosomal dysfunction and subsequent α-synuclein (α-Syn) accumulatio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt572
更新日期:2014-06-01 00:00:00
abstract::The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcri...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.5.525
更新日期:1993-05-01 00:00:00
abstract::Human gene expression traits have been shown to be dependent on gender, age and time of day in blood and other tissues. However, other factors that may impact gene expression have not been systematically explored. For example, in studies linking blood gene expression to obesity related traits, whether the fasted or fe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp476
更新日期:2010-01-01 00:00:00
abstract::The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently has been demonstrated to have an elevated frequency in Alzheimer's disease (AD) patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when compared with a control population. We therefore genotyped a large series of path...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.5.937
更新日期:1998-05-01 00:00:00
abstract::Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connec...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx110
更新日期:2017-06-15 00:00:00
abstract::Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 def...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx373
更新日期:2017-12-15 00:00:00
abstract::Mitochondrial dysfunction and oxidative stress are central to the molecular pathology of many human diseases. Riboflavin responsive multiple acyl-CoA dehydrogenation deficiency (RR-MADD) is in most cases caused by variations in the gene coding for electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Curr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu146
更新日期:2014-08-15 00:00:00
abstract::Niemann-Pick type C (NPC) disease is a fatal recessively inherited lysosomal cholesterol-sphingolipidosis. Mutations in the NPC1 gene cause approximately 95% of the cases, the rest being caused by NPC2 mutations. Here the molecular basis of a severe infantile form of the disease was dissected. The level of NPC1 protei...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg025
更新日期:2003-02-01 00:00:00
abstract::The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identifi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg111
更新日期:2003-05-01 00:00:00
abstract::The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chines...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw346
更新日期:2016-12-15 00:00:00
abstract::The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineag...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr069
更新日期:2011-05-15 00:00:00
abstract::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt364
更新日期:2013-10-15 00:00:00
abstract::In studies of genomic imprinting in the Prader-Willi/Angelman domain, an agouti coat color cassette was inserted into the downstream open reading frame (ORF) of the imprinted bicistronic Snurf-Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf-Snrpn, and produced a tan abdomen only when inh...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.14.1659
更新日期:2002-07-01 00:00:00
abstract::The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression pro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr328
更新日期:2011-10-15 00:00:00
abstract::Fragile X syndrome is the most frequent cause of heritable mental retardation. Most patients have a mutation in the 5' untranslated region of the FMR1 gene, consisting of the amplification of a polymorphic (CGG)nrepeat sequence, and cytogenetically express the folate-sensitive fragile site FRAXA in Xq27.3. Fragile X p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.109
更新日期:1998-01-01 00:00:00
abstract::Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu190
更新日期:2014-09-15 00:00:00
abstract::Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.12.2069
更新日期:1997-11-01 00:00:00
abstract::Induced pluripotent stem cell (iPSC)-derived cortical neurons potentially present a powerful new model to understand corticogenesis and neurological disease. Previous work has established that differentiation protocols can produce cortical neurons, but little has been done to characterize these at cellular resolution....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv637
更新日期:2016-03-01 00:00:00
abstract::Coproporphyrinogen oxidase is a mitochondrial heme-biosynthetic enzyme that converts coproporphyrinogen to protoporphyrinogen. Inherited deficiency of this enzyme causes the human genetic disease hereditary coproporphyria. Recently, we isolated, sequenced and expressed the cDNA encoding human coproporphyrinogen oxidas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.3.477
更新日期:1994-03-01 00:00:00