Abstract:
:Evidence is mounting that LRRK2 function, particularly its kinase activity, is elevated in multiple forms of Parkinson's disease, both idiopathic as well as familial forms linked to mutations in the LRRK2 gene. However, sensitive quantitative markers of LRRK2 activation in clinical samples remain at the early stages of development. There are several measures of LRRK2 activity that could potentially be used in longitudinal studies of disease progression, as inclusion/exclusion criteria for clinical trials, to predict response to therapy, or as markers of target engagement. Among these are levels of LRRK2, phosphorylation of LRRK2 itself, either by other kinases or via auto-phosphorylation, its in vitro kinase activity, or phosphorylation of downstream substrates. This is advantageous on many levels, in that multiple indices of elevated kinase activity clearly strengthen the rationale for targeting this kinase with novel therapeutic candidates, and provide alternate markers of activation in certain tissues or biofluids for which specific measures are not detectable. However, this can also complicate interpretation of findings from different studies using disparate measures. In this review we discuss the current state of LRRK2-focused biomarkers, the advantages and disadvantages of the current pallet of outcome measures, the gaps that need to be addressed, and the priorities that the field has defined.
journal_name
Front Neuroscijournal_title
Frontiers in neuroscienceauthors
Rideout HJ,Chartier-Harlin MC,Fell MJ,Hirst WD,Huntwork-Rodriguez S,Leyns CEG,Mabrouk OS,Taymans JMdoi
10.3389/fnins.2020.00865subject
Has Abstractpub_date
2020-08-18 00:00:00pages
865eissn
1662-4548issn
1662-453Xjournal_volume
14pub_type
杂志文章,评审abstract::D-norpseudoephedrine (NPE), also known as cathine, is found naturally in the shrub Catha edulis "Khat." NPE has been widely used as an appetite suppressant for the treatment of obesity. Although it is known that NPE acts on α1-adrenergic receptors, there is little information about the role of dopamine receptors on NP...
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abstract:Purpose:Maternal and postnatal diets result in long-term changes in offspring brain and behavior; however, the key mediators of these developmental changes are not well-defined. In this study, we investigated the impact of maternal and post-weaning high-fat diets on gene expression of key components mediating hippocamp...
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abstract::Recent studies suggest cone degeneration in retinitis pigmentosa (RP) may result from intracellular energy depletion. We tested the hypothesis that cones die when depleted of energy by examining the effect of two bioenergetic, nutraceutical agents on cone survival. The study had three specific aims: firstly, we, studi...
journal_title:Frontiers in neuroscience
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doi:10.3389/fnins.2019.01234
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abstract::The decoding of selective auditory attention from noninvasive electroencephalogram (EEG) data is of interest in brain computer interface and auditory perception research. The current state-of-the-art approaches for decoding the attentional selection of listeners are based on linear mappings between features of sound s...
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abstract::The fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates mRNA metabolism. FMRP has been largely studied in the brain, where the absence of this protein leads to fragile X syndrome, the most frequent form of inherited intellectual disability. Since the identification of the FMRP gene in ...
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abstract::Neurodegenerative diseases, including Alzheimer, Parkinson, Huntington, and amyotrophic lateral sclerosis, are a prominent class of neurological diseases currently without a cure. They are characterized by an inexorable loss of a specific type of neurons. The selective vulnerability of specific neuronal clusters (typi...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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abstract::Oligodendrocyte precursor cells (OPCs), also known as NG2 glia, arise from neural progenitor cells in the embryonic ganglionic eminences that also generate inhibitory neurons. They are ubiquitously distributed in the central nervous system, remain proliferative through life, and generate oligodendrocytes in both gray ...
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abstract::Possible risks stemming from the employment of novel, micrometer-thin printed electrodes for direct current neural stimulation are discussed. To assess those risks, electrochemical methods are used, including cyclic voltammetry, square-wave voltammetry, and electrochemical impedance spectroscopy. Experiments were cond...
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abstract::We investigated whether the categorical perception (CP) of speech might also provide a mechanism that aids its perception in noise. We varied signal-to-noise ratio (SNR) [clear, 0 dB, -5 dB] while listeners classified an acoustic-phonetic continuum (/u/ to /a/). Noise-related changes in behavioral categorization were ...
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abstract::Evidence obtained in recent years in a few species, especially rainbow trout, supports the presence in fish of nutrient sensing mechanisms. Glucosensing capacity is present in central (hypothalamus and hindbrain) and peripheral [liver, Brockmann bodies (BB, main accumulation of pancreatic endocrine cells in several fi...
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doi:10.3389/fnins.2015.00033
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journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2018.00699
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abstract::The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. Elk-1 is associated with a dimer of serum response factor (SRF) at the SRE site, and its phosphorylation occurs at specific residues in response...
journal_title:Frontiers in neuroscience
pub_type: 杂志文章
doi:10.3389/fnins.2011.00035
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abstract::HIGHLIGHTS Many AD target combinations are being explored for multi-target drug design.New databases and models increase the potential of computational drug designLiraglutide and other antidiabetics are strong candidates for repurposing to AD.Donecopride a dual 5-HT/AChE inhibitor shows promise in pre-clinical studies...
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abstract::In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings w...
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journal_title:Frontiers in neuroscience
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abstract::The cocaine- and amphetamine-regulated transcript (CART) has been the subject of significant interest for over a decade. Work to decipher the detailed mechanism of CART function has been hampered by the lack of specific pharmacological tools like antagonists and the absence of a specific CART receptor(s). However, ext...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,撤回出版物
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