Abstract:
:In the field of Parkinson's disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For over 10 years, the identification of a bona fide substrate and a physiological function for LRRK2 has been elusive, and only recently, Rab GTPases were identified as substrates for LRRK2 kinase activity. Additionally, LRRK2 gene expression data shows that LRRK2 is expressed at low levels in neurons and at high levels in cells of the immune system. These findings shifted research efforts from neuronal toxicity of LRRK2 mutations to the function of LRRK2 in both vesicle trafficking and the immune system, which has resulted in novel insights into the role of LRRK2 during infection and immunity. In this Perspective, we summarize the latest findings highlighting LRRK2 as a central regulator of vesicular trafficking, infection, immunity, and inflammation, speculating how LRRK2 function could influence neuronal pathology in PD.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Herbst S,Gutierrez MGdoi
10.1021/acsinfecdis.9b00051subject
Has Abstractpub_date
2019-06-14 00:00:00pages
809-815issue
6issn
2373-8227journal_volume
5pub_type
杂志文章abstract::Computer-aided screening of antimicrobial peptides (AMPs) is a promising approach for discovering novel therapies against multidrug-resistant bacterial infections. Here, we functionally and structurally characterized an Escherichia coli-derived AMP (EcDBS1R5) previously designed through pattern identification [α-helic...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00219
更新日期:2018-12-14 00:00:00
abstract::The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development ne...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00235
更新日期:2018-05-11 00:00:00
abstract::The α-Gal antigen [Galα(1,3)Galβ(1,4)GlcNAcα] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of α-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Ch...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00114
更新日期:2016-12-09 00:00:00
abstract::Dysentery is a major health threat that dramatically impacts childhood morbidity and mortality in developing countries. Various pathogenic agents cause dysentery, such as Shigella spp. and Escherichia coli, which are very closely related if not identical species. Sensitive and precise detection and identification of t...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00199
更新日期:2019-11-08 00:00:00
abstract::The maintenance of deoxyribonucleotide triphosphate (dNTP) homeostasis through synthesis and degradation is critical for accurate genomic and mitochondrial DNA replication fidelity. Trypanosoma brucei makes use of both the salvage and de novo pathways for the provision of pyrimidine dNTPs. In this respect, the sterile...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00551
更新日期:2021-01-08 00:00:00
abstract::The enzyme N-myristoyltransferase (NMT) catalyzes the essential fatty acylation of substrate proteins with myristic acid in eukaryotes and is a validated drug target in the parasite Trypanosoma brucei, the causative agent of African trypanosomiasis (sleeping sickness). N-Myristoylation typically mediates membrane loca...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00034
更新日期:2016-06-10 00:00:00
abstract::Three O. volvulus immunogenic peptide sequences recently discovered by peptide microarray were adapted to a lateral flow assay (LFA). The LFA employs gold nanoshells as novel high-contrast reporter nanoparticles and detects a serological response against the 3 peptides, found in OvOC9384, OvOC198, and OvOC5528, respec...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00031
更新日期:2018-06-08 00:00:00
abstract::Hypervirulent Klebsiella pneumoniae (hvKp) is an underrecognized pathotype of K. pneumoniae since the majority of cases have occurred in East Asia. However, hvKp is a public health threat due to its ability to infect healthy individuals, ongoing dissemination, and acquisition of resistance determinants. hvKp-directed ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00117
更新日期:2019-07-12 00:00:00
abstract::Bacterial quorum sensing (QS) is being contemplated as a promising target for developing innovative diagnostic and therapeutic strategies. Here we report for the first time the development of antibodies against 2-heptyl-4-quinolone (HHQ), a signaling molecule from the pqs QS system of Pseudomonas aeruginosa, involved ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00604
更新日期:2020-12-11 00:00:00
abstract::Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (M...
journal_title:ACS infectious diseases
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acsinfecdis.0c00291
更新日期:2020-07-10 00:00:00
abstract::Although many new anti-infectives have been discovered and developed solely using phenotypic cellular screening and assay optimization, most researchers recognize that structure-guided drug design is more practical and less costly. In addition, a greater chemical space can be interrogated with structure-guided drug de...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.7b00276
更新日期:2018-03-09 00:00:00
abstract::In order to identify the most attractive starting points for drugs that can be used to prevent malaria, a diverse chemical space comprising tens of thousands to millions of small molecules may need to be examined. Achieving this throughput necessitates the development of efficient ultra-high-throughput screening metho...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00143
更新日期:2016-04-08 00:00:00
abstract::Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellani...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00263
更新日期:2019-12-13 00:00:00
abstract::The increasing problem of multidrug resistance (MDR) in bacteria calls for discovery of new molecules and diagnostic methodologies that are effective against a wide range of microbial pathogens. We have studied the role of alexidine dihydrochloride (alex) as a bioaffinity ligand against lipopolysaccharide (LPS), a pat...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00087
更新日期:2018-11-09 00:00:00
abstract::The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular spa...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00075
更新日期:2016-12-09 00:00:00
abstract::Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral re...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00053
更新日期:2015-08-14 00:00:00
abstract::Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of Staphylococcus aureus SrtA by screening a library of...
journal_title:ACS infectious diseases
pub_type: 信件
doi:10.1021/acsinfecdis.9b00265
更新日期:2020-02-14 00:00:00
abstract::Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an O-acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00378
更新日期:2021-01-29 00:00:00
abstract::Enterovirus D68 (EV-D68) is an RNA virus that causes respiratory illnesses mainly in children. In severe cases, it can lead to neurological complications such as acute flaccid myelitis (AFM). EV-D68 belongs to the enterovirus genera of the Picornaviridae family, which also includes many other significant human pathoge...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00120
更新日期:2020-07-10 00:00:00
abstract::Amonabactins are a group of four related catecholate siderophores produced by several species of the genus Aeromonas, including A. hydrophila and the fish pathogen A. salmonicida subsp. salmonicida. Although the gene cluster encoding amonabactin biosynthesis also contains a gene that could encode the ferri-siderophore...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00274
更新日期:2019-11-08 00:00:00
abstract::Intravenous artesunate is effective against cerebral malaria (CM), but high mortality and neurological sequelae in survivors are inevitable. We investigated the effect of combined artesunate and tetramethylpyrazine using mouse models of experimental cerebral malaria (ECM). Artesunate + tetramethylpyrazine reduced micr...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00124
更新日期:2020-09-11 00:00:00
abstract::Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00245
更新日期:2019-04-12 00:00:00
abstract::Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgenc...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00211
更新日期:2018-04-13 00:00:00
abstract::Nucleic acid polymers (NAPs) are broad spectrum antiviral agents whose antiviral activity in hepatitis B virus (HBV) infection is derived from their ability to block the release of the hepatitis B virus surface antigen (HBsAg). This pharmacological activity blocks replenishment of HBsAg in the circulation, allowing ho...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.8b00156
更新日期:2019-05-10 00:00:00
abstract::At present, there is no licensed antiviral drug against dengue virus (DENV) infection. Mouse models of DENV infection have been widely used for preclinical evaluation of antivirals. However, only in a few instances so far have the data obtained from preclinical mouse model testing been associated with data from clinic...
journal_title:ACS infectious diseases
pub_type: 杂志文章,评审
doi:10.1021/acsinfecdis.8b00054
更新日期:2018-07-13 00:00:00
abstract::Vaccines and antivirals to combat dengue, Zika, and other flavivirus pathogens present a major, unmet medical need. Vaccine development has been severely challenged by the antigenic diversity of these viruses and the propensity of non-neutralizing, cross-reactive antibodies to facilitate cellular infection and increas...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00322
更新日期:2019-03-08 00:00:00
abstract::Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gi...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00032
更新日期:2019-08-09 00:00:00
abstract::Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillb...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00064
更新日期:2017-08-11 00:00:00
abstract::Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A frac...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00005
更新日期:2015-04-10 00:00:00
abstract::To explore the possibility of constrained peptides to target Plasmodium-infected cells, we designed a J domain mimetic derived from Plasmodium falciparum calcium-dependent protein kinase 1 ( PfCDPK1) as a strategy to disrupt J domain binding and inhibit PfCDPK1 activity. The J domain disruptor (JDD) peptide was confor...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00347
更新日期:2019-04-12 00:00:00