Abstract:
:The heroin analogue 1-methyl-4-phenylpyridinium, MPP(+), both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, Abeta(1-42), is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM d-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP(+) toxicity and hippocampal neurons from Abeta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration.
journal_name
Proc Natl Acad Sci U S Aauthors
Kashiwaya Y,Takeshima T,Mori N,Nakashima K,Clarke K,Veech RLdoi
10.1073/pnas.97.10.5440keywords:
subject
Has Abstractpub_date
2000-05-09 00:00:00pages
5440-4issue
10eissn
0027-8424issn
1091-6490pii
97/10/5440journal_volume
97pub_type
杂志文章abstract::Three distinct endosomal fractions were isolated in high purity from livers of estradiol-treated rats. Each fraction had characteristic physical and ultrastructural properties, but the lipid composition and major proteins of their membranes were similar and differed from those derived from the Golgi apparatus. Injecte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.19.6785
更新日期:1987-10-01 00:00:00
abstract::As root symbionts of cycad trees, cyanobacteria of the genus Nostoc produce beta-methylamino-l-alanine (BMAA), a neurotoxic nonprotein amino acid. The biomagnification of BMAA through the Guam ecosystem fits a classic triangle of increasing concentrations of toxic compounds up the food chain. However, because BMAA is ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0404926101
更新日期:2004-08-17 00:00:00
abstract::In budding yeast, two transcription factors, Swi4 and Swi6, control the expression of important cell cycle regulatory proteins (the G1 cyclins, Cln1 and Cln2, and the cyclin-like Hcs26) as well as the HO gene, whose product initiates mating-type switching. Both Swi4 and Swi6 are components of a protein complex that fo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.24.11852
更新日期:1992-12-15 00:00:00
abstract::[3H]Forskolin bound to high- and low-affinity sites in the rat brain. The high-affinity site was discretely located, with highest densities in the striatum, nucleus accumbens, olfactory tubercule, substantia nigra, hippocampus, and the molecular layers of the cerebellum. This site did not correlate well with the distr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.9.3216
更新日期:1988-05-01 00:00:00
abstract::S-adenosyl-L-methionine (SAM)-dependent O-methyltransferases (OMTs) catalyze the methylation of hydroxycinnamic acid derivatives for the synthesis of methylated plant polyphenolics, including lignin. The distinction in the extent of methylation of lignins in angiosperms and gymnosperms, mediated by substrate-specific ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.10.5461
更新日期:1997-05-13 00:00:00
abstract::Preparations of partially purified chloroplast DNA-dependent RNA polymerase from maize and some other plants transcribe cloned chloroplast genes preferentially and much more actively from appropriately negatively supercoiled templates than from relaxed templates. We have found that the polymerase in such fractions doe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.3.876
更新日期:1989-02-01 00:00:00
abstract::Human tuberculosis is caused by members of the Mycobacterium tuberculosis complex (MTBC) that vary in virulence and transmissibility. While genome-wide association studies have uncovered several mutations conferring drug resistance, much less is known about the factors underlying other bacterial phenotypes. Variation ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1915551117
更新日期:2020-04-14 00:00:00
abstract::Long-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell synapses must be balanced by long-term potentiation (LTP) to prevent saturation and allow reversal of motor learning. The only previously analyzed form of cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not nitric oxide...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.122206399
更新日期:2002-06-11 00:00:00
abstract::A phylogeny of marine Rhodophyta has been inferred by a number of methods from nucleotide sequences of nuclear genes encoding small subunit rRNA from 39 species in 15 orders. Sequence divergences are relatively large, especially among bangiophytes and even among congeners in this group. Subclass Bangiophycidae appears...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.15.7276
更新日期:1994-07-19 00:00:00
abstract::Individual proteins can now often be modified with atomic precision, but there are still major obstacles to connecting proteins into larger assemblies. To direct protein assembly, ideally, peptide tags would be used, providing the minimal perturbation to protein function. However, binding to peptides is generally weak...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1315776111
更新日期:2014-04-01 00:00:00
abstract::Metalloproteases from at least two Gram-negative organisms selectively hydrolyze the surface of human fixed washed platelets. The protease-treated platelets lose their ability to aggregate with bovine von Willebrand factor and human von Willebrand factor plus ristocetin. The present study reports the membrane glycopro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.5.1433
更新日期:1982-03-01 00:00:00
abstract::A protein factor that participates in the formation of a covalent complex between the 80,000-dalton precursor of the adenovirus (Ad) terminal protein (pTP) and 5'-dCMP has been isolated and characterized. This 47,000-dalton protein, isolated from nuclear extracts of uninfected HeLa cells, has been designated nuclear f...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.21.6438
更新日期:1982-11-01 00:00:00
abstract::Fatty acid transport protein 4 (FATP4), a transmembrane protein in the endoplasmic reticulum (ER), is a recently identified negative regulator of the ER-associated retinal pigment epithelium (RPE)65 isomerase necessary for recycling 11-cis-retinal, the light-sensitive chromophore of both rod and cone opsin visual pigm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2012623117
更新日期:2020-12-15 00:00:00
abstract::In eukaryotes, microtubules are essential for cellular plasticity and dynamics. Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated acetyltransferase, acts as a negative modulator of microtubule stability through acetylation of EB1, a protein that controls the plus ends of microtubules. PCAF ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1202639109
更新日期:2012-10-09 00:00:00
abstract::With threats to nature becoming increasingly prominent, in order for biodiversity levels to persist, there is a critical need to improve implementation of conservation measures. In the oceans, the surveillance of fisheries is complex and inadequate, such that quantifying and locating nondeclared and illegal fisheries ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1915499117
更新日期:2020-02-11 00:00:00
abstract::Humans reason about the mental states of others; this capacity is called Theory of Mind (ToM). In typically developing adults, ToM is supported by a consistent group of brain regions: the bilateral temporoparietal junction (TPJ), medial prefrontal cortex (MPFC), precuneus (PC), and anterior temporal sulci (aSTS). How ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900010106
更新日期:2009-07-07 00:00:00
abstract::Peripheral inhibitory nerves are physiological regulators of the contractile behavior of visceral smooth muscles. One of the transmitters responsible for inhibitory neurotransmission has been reputed to be a purine, possibly ATP. However, the exact identity of this substance has never been verified. Here we show that ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705510104
更新日期:2007-10-09 00:00:00
abstract::In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr. (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation method to show that healthy adults harbor a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.26.14894
更新日期:1997-12-23 00:00:00
abstract::A strong mutator effect has been observed in Escherichia coli K-12 strains mutated in the bglY gene (27 min). The frequency of point mutations is not modified in bglY mutant strains. In contrast, a strong increase in spontaneous generation of large deletions has been observed in these strains, both for chromosomal mar...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.1.360
更新日期:1990-01-01 00:00:00
abstract::Gene expression has a stochastic component because of the single-molecule nature of the gene and the small number of copies of individual DNA-binding proteins in the cell. We show how the statistics of such systems can be mapped onto quantum many-body problems. The dynamics of a single gene switch resembles the spin-b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2627987100
更新日期:2003-03-04 00:00:00
abstract::Interactions between two excitatory monosynaptic inputs to hippocampal neurons of the CA1 region were examined in the in vitro slice. By adjusting the strengths of the electrical stimuli delivered to the two input pathways, one was made to generate a weak and the other a strong synaptic response. Simultaneous tetanic ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.23.7347
更新日期:1983-12-01 00:00:00
abstract::A key feature of immune evasion for African trypanosomes is the functional specialization of their surface membrane in an invagination known as the flagellar pocket (FP), the cell's sole site of endocytosis and exocytosis. The FP membrane is biochemically distinct yet continuous with those of the cell body and the fla...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0909289106
更新日期:2009-10-13 00:00:00
abstract::Prenylated Rab GTPases regulate intracellular vesicle trafficking in eukaryotic cells by associating with specific membranes and recruiting a multitude of Rab-specific effector proteins. Prenylation, membrane delivery, and recycling of all 60 members of the Rab GTPase family are regulated by two related molecules, Rab...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0701817104
更新日期:2007-07-24 00:00:00
abstract::We have established a transformation system for Dictyostelium discoideum. The transformation vector contains the protein coding region of the Tn5 neomycin resistance gene fused to the proposed promoter of the Dictyostelium actin 8 gene; the vector also contains a sequence that acts as an autonomously replicating seque...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.23.7356
更新日期:1982-12-01 00:00:00
abstract::Midbrain dopamine (DA) neurons respond to sensory stimuli associated with future rewards. When reward is delivered probabilistically, DA neurons reflect this uncertainty by increasing their firing rates in a period between the sensory cue and reward delivery time. Probability of reward, however, has been externally co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1117636108
更新日期:2011-12-06 00:00:00
abstract::The multifunctional Ca2+/calmodulin-dependent protein kinase purified from rat brain cytosol undergoes an intramolecular self-phosphorylation or autophosphorylation. Autophosphorylation produces two strikingly different effects on kinase activity that are dependent on the level of ATP used in the reaction. At low but ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.24.9497
更新日期:1986-12-01 00:00:00
abstract::Transcription antitermination by lambda N gene product is affected in a mutant Escherichia coli with altered ribosomal protein S10, caused by the nusE71 mutation. To study the role of translation in antitermination, we have fused the phage nutR locus, the site of action of N, with the lac regulatory region. We have mo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.12.3612
更新日期:1984-06-01 00:00:00
abstract::Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressur...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1617849114
更新日期:2017-01-31 00:00:00
abstract::Serum from a patient (CO) with acute lymphoblastic leukemia was reactive in immunoadherence assays with autologous leukemia cells but not with autologous blood lymphocytes or bone marrow cells during complete remission. Extensive absorption tests with an array of leukemia cells and normal cells were performed in order...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.8.2341
更新日期:1983-04-01 00:00:00
abstract::Untargeted metabolomics of environmental samples routinely detects thousands of small molecules, the vast majority of which cannot be identified. Meta-mass shift chemical (MeMSChem) profiling was developed to identify mass differences between related molecules using molecular networks. This approach illuminates metabo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1710248114
更新日期:2017-10-31 00:00:00