Abstract:
:LRRK2 mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamatergic axons, and its levels rise developmentally coincident with glutamatergic synapse formation. The onset and timing of expression suggests strongly that LRRK2 regulates the development, maturation and function of synapses. Several lines of data in mice show that LRRK2-G2019S, the most common LRRK2 mutation, produces an abnormal gain of pathological function that affects synaptic activity, spine morphology, persistent forms of synapse plasticity and behavioral responses to social stress. Effects of the mutation can be detected as early as the second week of postnatal development and can last or have consequences that extend into adulthood and occur in the absence of dopamine loss. These data suggest that the generation of neural circuits that support complex behaviors is modified by LRRK2-G2019S. Whether such alterations impart vulnerability to neurons directly or indirectly, they bring to the forefront the idea that neural circuits within which dopamine neurons eventually degenerate are assembled and utilized in ways that are distinct from circuits that lack this mutation and may contribute to non-motor symptoms observed in humans with PD.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Benson DL,Matikainen-Ankney BA,Hussein A,Huntley GWdoi
10.1042/BST20180468subject
Has Abstractpub_date
2018-12-17 00:00:00pages
1697-1705issue
6eissn
0300-5127issn
1470-8752pii
BST20180468journal_volume
46pub_type
杂志文章,评审abstract::Post-translational modification (PTM) of histones has been investigated in eukaryotes for years, revealing its widespread occurrence and functional importance. Many PTMs affect chromatin folding and gene activity. Only recently the occurrence of such modifications has been recognized in bacteria. However, it is unclea...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180488
更新日期:2018-10-19 00:00:00
abstract::Microscopes are used to characterize small objects with the help of probes that interact with the specimen, such as photons and electrons in optical and electron microscopies, respectively. In atomic force microscopy (AFM), the probe is a nanometric tip located at the end of a microcantilever which palpates the specim...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160316
更新日期:2017-04-15 00:00:00
abstract::Anaphase B spindle elongation plays an important role in chromosome segregation. In the present paper, we discuss our model for anaphase B in Drosophila syncytial embryos, in which spindle elongation depends on an ip (interpolar) MT (microtubule) sliding filament mechanism generated by homotetrameric kinesin-5 motors ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0391149
更新日期:2011-10-01 00:00:00
abstract::Similar changes in glycosylation occur in the colonic epithelium in inflammatory conditions such as ulcerative colitis and Crohn's disease and also in colon cancer and precancerous adenomatous polyps. They include reduced length of O-glycans, reduced sulfation, increased sialylation and increased expression of oncofet...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0361482
更新日期:2008-12-01 00:00:00
abstract::Animal venoms are recognised as unique biological systems in which to study molecular evolution. Venom use has evolved numerous times among the insects, and insects today use venom to capture prey, defend themselves from predators, or to subdue and modulate host responses during parasitism. However, little is known ab...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190820
更新日期:2020-08-28 00:00:00
abstract::The protein kinase C (PKC) family of serine/threonine protein kinases share structural homology, while exhibiting substantial functional diversity. PKC isoforms are ubiquitously expressed in tissues which makes it difficult to define roles for individual isoforms, with complexity compounded by the finding that PKC iso...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140255
更新日期:2014-12-01 00:00:00
abstract::The XMAP215 (Xenopus microtubule-associated protein 215) and CLASP [CLIP-170 (cytoskeletal linker protein 170) associated protein] microtubule plus end tracking families play central roles in the regulation of interphase microtubule dynamics and the proper formation of mitotic spindle architecture and flux. XMAP215 me...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0371002
更新日期:2009-10-01 00:00:00
abstract::Mitogenic tyrosine kinase receptors such as the EGFR (epidermal growth factor receptor) are endocytosed once they are activated at the cell surface. After reaching the early endosome, they are ubiquitinated within their cytosolic domain and are consequently sorted away from recycling receptors. They are then incorpora...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370146
更新日期:2009-02-01 00:00:00
abstract::This review focuses on recent insights into the mechanisms and the biological functions of the proteasome. This large ATP-dependent proteolytic complex is the main site for protein degradation in mammalian cells and catalyses the rapid degradation of ubiquitinated proteins, and is the source of most antigenic peptides...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0350012
更新日期:2007-02-01 00:00:00
abstract::Ligand-gated ion channels function as rapid signal transducers, converting chemical signals (in the form of neurotransmitters) into electrical signals in the postsynaptic neuron. This is achieved by the recognition of neurotransmitter at its specific-binding sites, which then triggers the opening of an ion channel ('g...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320540
更新日期:2004-06-01 00:00:00
abstract::The function of biomolecules is intrinsically linked to their structure and the complexes they form during function. Techniques for the determination of structures and dynamics of these nanometre assemblies are therefore important for an understanding on the molecular level. PELDOR (pulsed electron-electron double res...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0390128
更新日期:2011-01-01 00:00:00
abstract::MAPK (mitogen-activated protein kinase) signalling pathways contribute to the regulation of diverse responses, including normal and pathological aspects of cell growth, division, differentiation and death. Their ubiquity and versatility raise the issue of how they achieve specific coupling of signal with cellular resp...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0340837
更新日期:2006-11-01 00:00:00
abstract::Effective stroke therapies require recanalization of occluded cerebral blood vessels; however, early reperfusion can cause BBB (blood-brain barrier) injury, leading to cerebral oedema and/or devastating brain haemorrhage. These complications of early reperfusion, which result from excess production of ROS (reactive ox...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0341366
更新日期:2006-12-01 00:00:00
abstract::One of the primary functions of AMP-activated protein kinase (AMPK) is to regulate the metabolic pathways in response to reduced cellular energy charge. Most of the known targets of the kinase are cytoplasmic enzymes involved in both catabolic and anabolic metabolism. In addition, activation of AMPK in many cells resu...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310224
更新日期:2003-02-01 00:00:00
abstract::A range of mitochondria-targeted probe molecules that comprise a lipophilic cation covalently attached to an active moiety have been developed. The lipophilic cation causes the accumulation of these molecules into mitochondria, driven by the mitochondrial membrane potential. To date, we have targeted antioxidants, spi...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0321011
更新日期:2004-12-01 00:00:00
abstract::The 'fusion peptides' of a group of enveloped viruses that includes influenza, paramyxo-, retro-and filo-viruses are N-terminal regions of their membrane fusion proteins generated by cleavage of non-functional precursors. For the influenza membrane fusion protein, haemagglutinin (HA), the three-dimensional structures ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0290623
更新日期:2001-08-01 00:00:00
abstract::Glycosaminoglycans (GAGs), present in the extracellular matrix, are exploited by numerous, distinct microbes for cellular attachment, adhesion, invasion and evasion of the host immune system. Glycosaminoglycans, including the widely used, clinical anticoagulant heparin and semi-synthetic analogues thereof, have been r...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20170404
更新日期:2018-08-20 00:00:00
abstract::Fibrotic disorders of the liver, kidney and lung are associated with excessive deposition of extracellular matrix proteins and ongoing coagulation-cascade activity. In addition to their critical roles in blood coagulation, thrombin and the immediate upstream coagulation proteases, Factors Xa and VIIa, influence numero...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/
更新日期:2002-04-01 00:00:00
abstract::[Ca(2+)](i) (intracellular Ca(2+) concentration) oscillations play a central role in the activation of T-lymphocytes by antigen. Oscillations in T-cells are absolutely dependent on Ca(2+) influx through store-operated CRAC channels (Ca(2+)-release-activated Ca(2+) channels), and evidence suggests that they arise from ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310925
更新日期:2003-10-01 00:00:00
abstract::DNA topology changes dynamically during DNA replication. Supercoiling, precatenation, catenation and knotting interplay throughout the process that is finely regulated by DNA topoisomerases. In the present article, we provide an overview of theoretical and experimental approaches to understand the interplay between va...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120281
更新日期:2013-04-01 00:00:00
abstract::Shewanella oneidensis MR-1 is a sediment organism capable of dissimilatory reduction of insoluble metal compounds such as those of Fe(II) and Mn(IV). This bacterium has been used as a model organism for potential applications in bioremediation of contaminated environments and in the production of energy in microbial f...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120114
更新日期:2012-12-01 00:00:00
abstract::Enzymes of the 1-deoxy-D-xylulose 5-phosphate/2-C-methylerythritol 4-phosphate (DOXP/MEP) pathway are targets for new herbicides and antibacterial drugs. Until now, no inhibitors for the DOXP synthase have been known of. We show that one of the breakdown products of the herbicide clomazone affects the DOXP synthase. O...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Much work has gone into understanding the physical basis of the enormous catalytic power of enzymes over the last 50 years or so. Nevertheless, the detailed mechanism used by Nature's catalysts to speed chemical transformations remains elusive. DHFR (dihydrofolate reductase) has served as a paradigm to study the relat...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370349
更新日期:2009-04-01 00:00:00
abstract::Findings from gene expression profiling studies are leading to new diagnostic and therapeutic strategies that can be applied in medical practice, especially in the field of oncology. Promising results of gene expression profiling of the peripheral blood in patients with ischaemic stroke have been obtained in recent pi...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341313
更新日期:2006-12-01 00:00:00
abstract::The discovery that nuclear factor erythroid 2-related factor 2 (Nrf2) undergoes translocational oscillations from cytoplasm to nucleus in human cells with frequency modulation linked to activation of a stress-stimulated cytoprotective response raises the prospect that the Nrf2 works mechanistically analogous to a wire...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20150060
更新日期:2015-08-01 00:00:00
abstract::A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug developme...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130233
更新日期:2014-04-01 00:00:00
abstract::Most research strategies for cartilage tissue engineering use extended culture with complex media loaded with costly GFs (growth factors) to drive tissue assembly and yet they result in the production of cartilage with inferior mechanical and structural properties compared with the natural tissue. Recent evidence sugg...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20140031
更新日期:2014-06-01 00:00:00
abstract::In fluctuating environmental conditions, organisms must modulate their bioenergetic production in order to maintain cellular homeostasis for optimal fitness. Mitochondria are hubs for metabolite and energy generation. Mitochondria are also highly dynamic in their function: modulating their composition, size, density, ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20200250
更新日期:2020-11-27 00:00:00
abstract::PABPs [poly(A)-binding proteins] bind to the poly(A) tail of eukaryotic mRNAs and are conserved in species ranging from yeast to human. The prototypical cytoplasmic member, PABP1, is a multifunctional RNA-binding protein with roles in global and mRNA-specific translation and stability, consistent with a function as a ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140111
更新日期:2014-08-01 00:00:00
abstract::The 26S proteasome is a non-lysosomal protease in the cytosol and nucleus of eukaryotic cells. Its main function is to mediate ubiquitin-dependent proteolysis. The 26S proteasome is a multimeric complex composed by the 20S proteasome CP (core particle) and the 19S RPs (regulatory particles). Although the atomic struct...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0380029
更新日期:2010-02-01 00:00:00