Abstract：
:Post-translational modifications of proteins are ubiquitous in living organisms, as they enable an accurate control of the interactions of these macromolecules. For mechanistic studies, it would be highly advantageous to be able to produce in vitro post-translationally modified proteins with site-specificity. Here, we demonstrate one facile way to achieve this goal through the use of post-translational chemical mutagenesis. We illustrate this approach by performing site-specific phosphorylation and methylation of tau, a protein that stabilizes microtubules and whose aggregation is closely linked with Alzheimer's disease. We then verify the effects of the post-translational modifications on the ability of tau to control microtubule polymerization, revealing in particular an unexpected role for phosphorylation at S199, which is outside the microtubule-binding region of tau. These results show how the chemical mutagenesis approach that we present enables the systematic analysis of site-specific post-translational modifications of a key protein involved in the pathogenesis of Alzheimer's disease.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Lindstedt PR,Taylor RJ,Bernardes GJL,Vendruscolo Mdoi
10.1021/acschemneuro.0c00761subject
Has Abstractpub_date
2021-01-19 00:00:00issn
1948-7193pub_type
杂志文章abstract：:Of the free-living amoebae (FLA) Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. are known to cause encephalitis. Coined with the term "brain-eating amoebae" (BEA), infection of the central nervous system with FLA has a high mortality rate. A combination of diagnostic delay, lack of new drug developm...
journal_title：ACS chemical neuroscience
pub_type： 社论
doi：10.1021/acschemneuro.9b00635
更新日期：2020-08-19 00:00:00
abstract：:Extensive experimental and computational studies have suggested that multiple Zn(2+) binding modes in amyloid β (Aβ) peptides could exist simultaneously. However, consistent results have not been obtained for the effects of Zn(2+) binding on Aβ structure, dynamics, and kinetics in particular. Some key questions such a...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn4001445
更新日期：2013-11-20 00:00:00
abstract：:Amyloid fibrils are the most distinct components of the plaques associated with various neurodegenerative diseases. Kinetic studies of amyloid fibril formation shed light on the microscopic mechanisms that underlie this process as well as the contributions of internal and external factors to the interplay between diff...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00104
更新日期：2015-08-19 00:00:00
abstract：:The permeation of the potassium ion (K+) through the selectivity filter (SF) of the large conductance Ca2+-activated potassium (Slo1) channel remains an interesting question to study. Although the mode of K+ entering and leaving the SF has been revealed, the mechanism of K+ passing through the SF is still not clear. I...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00215
更新日期：2019-08-21 00:00:00
abstract：:Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00612
更新日期：2021-01-20 00:00:00
abstract：:Gangliosides are biologically important glycolipids widely distributed in vertebrate cells. An important member of the ganglioside family is the monosialylganglioside GM1, which has been suggested as a potential therapeutic for Parkinson's disease. In the current study, a late-stage radiofluorination protocol was deve...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00161
更新日期：2020-05-06 00:00:00
abstract：:Single-cell mass spectrometry has become an established technique to study specific molecular properties such as the neuropeptide complement of identified neurons. Here, we describe a strategy to characterize, by MALDI-TOF mass spectrometry, neurochemical composition of neurons that were identified by their electrophy...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00163
更新日期：2018-08-15 00:00:00
abstract：:Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlyi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00078
更新日期：2017-09-20 00:00:00
abstract：:Botulinum neurotoxin (BoNT), the etiological agent that causes the neuroparalytic disease botulism, has become a highly studied drug target in light of the potential abuse of this toxin as a weapon of bioterrorism. In particular, small molecule inhibitors of the light chain metalloprotease of BoNT serotype A have rece...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn200021q
更新日期：2011-06-15 00:00:00
abstract：:Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, wh...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00060
更新日期：2015-06-17 00:00:00
abstract：:3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 doub...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00153
更新日期：2015-11-18 00:00:00
abstract：:The blood-brain barrier (BBB) is an important barrier that separates brain tissue from peripheral blood. The permeability of the BBB can be destroyed by external harmful factors, such as lipopolysaccharide (LPS), which contributes to neuroinflammation and central nervous system diseases. The present study aims to inve...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00537
更新日期：2020-12-16 00:00:00
abstract：:Genetically encoded tools are positioned to serve a unique and critical role in bridging the gap between the genetic identity of neurons and their functional properties. However, the use of these tools is limited by our current understanding of cell-type identity. As we make technological advances that focus on captur...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00008
更新日期：2015-01-21 00:00:00
abstract：:Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00224
更新日期：2017-10-18 00:00:00
abstract：:The understanding of the interaction between the membrane of neurons and amyloid-β peptides is of crucial importance to shed light on the mechanism of toxicity in Alzheimer's disease. This paper describes how supercritical angle fluorescence spectroscopy was applied to monitor in real-time the interaction between a su...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00264
更新日期：2019-12-18 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00226
更新日期：2017-10-18 00:00:00
abstract：:This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of th...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn200043e
更新日期：2011-08-17 00:00:00
abstract：:Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are in...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500258c
更新日期：2015-02-18 00:00:00
abstract：:Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble β-amyloid oligomer, which can induce neurotoxicity, is generally regarded as the main neurotoxin in Alzheimer's disease. Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, c...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00527
更新日期：2018-06-20 00:00:00
abstract：:Altered intestinal permeability has been correlated with Parkinson's pathophysiology in the enteric nervous system, before manifestations in the central nervous system (CNS). The inflammatory endotoxin or lipopolysaccharide (LPS) released by gut bacteria is known to modulate α-synuclein amyloidogenesis through the for...
journal_title：ACS chemical neuroscience
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doi：10.1021/acschemneuro.8b00733
更新日期：2019-05-15 00:00:00
abstract：:Glioblastoma multiforme, a type of deadly brain cancer, originates most commonly from astrocytes found in the brain. Current multimodal treatments for glioblastoma minimally increase life expectancy, but significant advancements in prognosis have not been made in the past few decades. Here we investigate cellular repr...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00365
更新日期：2018-12-19 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300036b
更新日期：2012-05-16 00:00:00
abstract：:We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00654
更新日期：2019-05-15 00:00:00
abstract：:Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation res...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00629
更新日期：2019-03-20 00:00:00
abstract：:γ-Secretase is a multiprotein complex that catalyzes intramembrane proteolysis associated with Alzheimer's disease and cancer. Here, we have developed potent sulfonamide clickable photoaffinity probes that target γ-secretase in vitro and in cells by incorporating various photoreactive groups and walking the clickable ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00127
更新日期：2016-08-17 00:00:00
abstract：:Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00074
更新日期：2018-07-18 00:00:00
abstract：:The finding that acetylcholinesterase (AChE) colocalizes with β-amyloid (Aβ) and promotes and accelerates Aβ aggregation has renewed an intense interest in developing new multifunctional AChE inhibitors as potential disease-modifying drugs for Alzheimer's therapy. To this end, we have developed a new class of selectiv...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100069c
更新日期：2010-11-17 00:00:00
abstract：:Aβ peptides, the main protein components of Alzheimer's disease (AD) plaques, derive from a proteolytic cleavage of the amyloid precursor protein. Due to heterogeneous cleavage sites, a series of Aβ peptides, including the major and widely studied species Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), are produced. In addition to t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00456
更新日期：2017-04-19 00:00:00
abstract：:Protein function depends on both protein structure and amino acid (aa) sequence. Here we show that modular features of both structure and function can be quantified economically from the aa sequences alone for the small (40,42 aa) plaque-forming (aggregative) amyloid beta fragments. Some edge and center features of th...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn5001793
更新日期：2015-05-20 00:00:00
abstract：:Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00343
更新日期：2017-11-15 00:00:00
