A5049290683- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Cellular transport and secretion
- Lysosomal Storage Disorders Research
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
- Autophagy in Disease and Therapy
- Banana Cultivation and Research
- Alzheimer's disease research and treatments
- Health and Medical Research Impacts
- Neurogenetic and Muscular Disorders Research
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- S100 Proteins and Annexins
- Glycosylation and Glycoproteins Research
- Amyotrophic Lateral Sclerosis Research
- Diversity and Career in Medicine
- DNA and Nucleic Acid Chemistry
- Nuclear Receptors and Signaling
- Protein Structure and Dynamics
- Plant Gene Expression Analysis
- History of Medical Practice
- RNA Research and Splicing
National Institutes of Health
2015-2023
National Institute on Aging
2017-2023
University of Arkansas for Medical Sciences
2018-2023
University College London
2022
Institute on Aging
2017-2021
University of Arkansas at Fayetteville
2012-2016
Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute the risk of disease, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA, LRRK2, GBA) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in GBA, encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as dementia. These variants,...
Studies of multiple neurodegenerative disorders have identified many genetic variants that are associated with risk disease throughout a lifetime. For example, Parkinson’s (PD) is attributed in part to both coding mutations the leucine-rich repeat kinase 2 ( LRRK2 ) gene and common noncoding variation 5′ region locus, as by genome-wide association studies (GWAS). However, mechanisms linking GWAS pathogenicity largely unknown. Here, we found influence PD-associated on expression specifically...
Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 parkin operate pathways that preserve mitochondrial integrity, but the function of DJ-1 how it relates to poorly understood. A series unbiased high-content screens were used analyze changes at protein, RNA, metabolite level rodent brains lacking Results validated using targeted approaches, cellular assays performed probe mechanisms involved. We find both rat mouse brains, knockout results an age-dependent...
Massive genetic analysis identifies critical pathways and cell types involved in pathogenesis of amyotrophic lateral sclerosis.
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson disease (PD), while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase activity and induce neurotoxicity vitro vivo. The small GTPase Rab8a is a substrate involved receptor-mediated recycling endocytic trafficking of transferrin, but the effect on function poorly understood. Here, we show that gain-of-function sequestration endogenous to lysosomes overexpression cell...
Article26 July 2021Open Access Source DataTransparent process LAG3 is not expressed in human and murine neurons does modulate α-synucleinopathies Marc Emmenegger orcid.org/0000-0002-6073-8811 Institute of Neuropathology, University Zurich, Switzerland These authors contributed equally to this work Search for more papers by author Elena De Cecco orcid.org/0000-0002-0148-2596 Marian Hruska-Plochan orcid.org/0000-0002-9253-4362 Department Quantitative Biomedicine, Timo Eninger German Center...
Abstract Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether associations are due to changes in cell numbers and/or per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) examine proportions...
Aromatic amino acids often flank the transmembrane alpha helices of integral membrane proteins. By favoring locations within membrane-water interface lipid bilayer, aromatic residues Trp, Tyr, and sometimes Phe may serve as anchors to help stabilize a orientation. In this work, we compare influence interfacial or upon properties tilted helical peptides. For such comparisons, it has been critical start with no more than one residue near each end helix, for example, that GWALP23...
Autosomal dominant mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD). Most pathogenic LRRK2 result amino acid substitutions the central ROC (Ras of complex proteins)–C-terminus ROC–kinase triple domain and affect enzymatic functions protein. However, there several variants LRRK2, including risk factor G2385R, that PD pathogenesis by unknown mechanisms. Previously, we have shown G2385R has decreased activity vitro altered affinity to interactors....
Abstract Mutations in the DJ-1 gene cause autosomal recessive parkinsonism humans. Several mouse models of deficiency have been developed, but they do not dopaminergic neuron cell death substantia nigra pars compacta (SNpc). Mitochondrial DNA (mtDNA) damage occurs frequently aged human SNpc SNpc. We hypothesized that reason -deficient mice is due to an absence mtDNA damage. tested this hypothesis by crossing with similar amounts their as humans ( Polg mutator mice). At 1 year age, we counted...
The American Association of Neurological Surgeons (AANS) Neurosurgery Research and Education Foundation (NREF) provides ongoing competitive research fellowships for residents young investigators. authors sought to determine the characteristics career tracks award recipients.
Abstract Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal dominant Parkinson’s disease (PD) while polymorphic LRRK2 variants are associated with sporadic PD. PD-linked mutations increase activity and induce neurotoxicity vitro vivo . The small GTPase Rab8a is a substrate involved receptor-mediated recycling endocytic trafficking of transferrin, but the effect on function poorly understood. Here, we show that gain-of-function sequestration endogenous into lysosomes cells...
Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with inherited forms of Parkinson's disease (PD), causing by a gain function. Here, we describe series isogenic iPSC lines any five pathogenic mutations (N1437H, R1441C, Y1699C, G2019S and I2020T); two hypothesis testing (GTP binding null, T1348N, dead, K1906M) LRRK2 knockouts. This resource could be used to assess effects on the function endogenous and/or study interactors substrates iPSC-derived cellular models.
The kinetic evaluation of several<italic>N</italic>-benzylgalactonoamidines identified<italic>p</italic>-methylbenzylgalactonoamidine as a putative transition state analog for the enzymatic hydrolysis β-galactopyranosides by β-galactosidase (<italic>A. oryzae</italic>).
Abstract Studies of the genetic basis Parkinson’s disease (PD) have identified many disease-associated variants, but mechanisms linking variants to pathogenicity are largely unknown. PD risk is attributed both coding mutations in Leucine-rich repeat kinase 2 ( LRRK2 ) gene and common non-coding variation upstream locus. Here we show that influence genotype at variant rs76904798 on expression propagated specifically through microglia, contrast evaluations based general rather than...
Objective: To objectively measure color vision dysfunction in idiopathic Parkinson's disease (iPD) using an easily administered, essentially free, modified Stroop test. Methods: 61 iPD patients and 26 age-matched controls (HC) were enrolled after IRB approval performed congruent (CST) incongruent (IST) tests consisting of 40 words 10 colors arranged a 5x8 grid. The scorer was blinded to participant diagnosis. Errors on IST defined as type 1 (written word reported rather than color) or 2...
ABSTRACT Despite the considerable progress in unraveling genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand molecular mechanisms underlying disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify biological pathways and cell types involved ALS. This data-driven identified multiple aspects biology disease that resolved into broader themes, namely neuron projection morphogenesis, membrane trafficking ,...