A5044342845- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Cellular transport and secretion
- Pain Mechanisms and Treatments
- Wnt/β-catenin signaling in development and cancer
- Seaweed-derived Bioactive Compounds
- Neuroscience and Neuropharmacology Research
- Astro and Planetary Science
- Trace Elements in Health
- Planetary Science and Exploration
- Cholinesterase and Neurodegenerative Diseases
- Neuropeptides and Animal Physiology
- Polysaccharides and Plant Cell Walls
- RNA Research and Splicing
- Prion Diseases and Protein Misfolding
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Enzyme Production and Characterization
- GABA and Rice Research
- RNA regulation and disease
- Protein Hydrolysis and Bioactive Peptides
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
The University of Texas Southwestern Medical Center
2014-2025
Southwestern Medical Center
2006-2024
Children's Research Hospital
2024
St. Jude Children's Research Hospital
2024
Banner Sun Health Research Institute
2024
Zhejiang Gongshang University
2021-2024
Jimei University
2019-2021
University of Jinan
2021
Chinese Academy of Fishery Sciences
2013-2020
Ministry of Agriculture and Rural Affairs
2020
TAR DNA-binding protein 43 (TDP-43) is associated with a spectrum of neurodegenerative diseases. Although TDP-43 resembles heterogeneous nuclear ribonucleoproteins, its RNA targets and physiological partners remain unknown. Here we identify from cortical neurons by immunoprecipitation followed deep sequencing (RIP-seq). The canonical binding site (TG)n 55.1-fold enriched, moreover, variant adenine in the middle, (TG)nTA(TG)m, highly abundant among reads our RIP-seq library. can be divided...
TDP-43, or TAR DNA-binding protein 43, is a pathological marker of spectrum neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 an RNA/DNA-binding implicated in transcriptional posttranscriptional regulation. Recent work also suggests that associates cytoplasmic stress granules, which are transient structures form response to stress. In this study, we establish sorbitol as novel physiological...
Murine models of Alzheimer's disease (AD) are crucial for elucidating mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse amyloidosis. We identified shared pathways by integrating with human metadata prioritized components multi-omics analysis. Collectively, two commonly used (5xFAD APP-KI) replicate 30% protein alterations; additional genetic incorporation...
The presenilin (PS) genes associated with Alzheimer disease encode polytopic transmembrane proteins which undergo physiologic endoproteolytic cleavage to generate stable NH<sub>2</sub>- and COOH-terminal fragments (NTF or CTF) co-localize in intracellular membranes, but are tightly regulated their stoichiometry abundance. We have used linear glycerol velocity discontinuous sucrose gradient analysis investigate the distribution native conformation of PS1 PS2 during this processing cultured...
Presenilin (PS, PS1/PS2) complexes are known to be responsible for the intramembranous γ-secretase cleavage of β-amyloid precursor protein and signaling receptor Notch. PS holoprotein undergoes endoproteolysis by an unknown enzymatic activity generate NH2- COOH-terminal fragments, a process that is required formation active stable PS/-γ-secretase complex. Biochemical genetic studies have recently identified nicastrin, APH-1, PEN-2 as essential cofactors physically interact with PS1 necessary...
Presenilin and nicastrin are essential components of the γ-secretase complex that is required for intramembrane proteolysis an increasing number membrane proteins including amyloid-β precursor protein (APP) Notch. By using co-immunoprecipitation nickel affinity pull-down approaches, we now show mammalian APH-1 (mAPH-1), a conserved multipass protein, physically associates with heterodimers presenilin amino- carboxyl-terminal fragments in human cell lines rat brain. Similar to loss...
Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal dementia, currently untreatable progressive neurodegenerative disease. By chemical library screening, we identified suberoylanilide hydroxamic acid (SAHA), Food and Drug Administration-approved histone deacetylase inhibitor, as an enhancer GRN expression. SAHA dose-dependently increased mRNA protein levels in cultured cells restored near-normal expression haploinsufficient from human subjects. Although...
Significance Both overexpression of wild-type fused in sarcoma (FUS) protein and missense mutations can be pathogenic a group related neurodegenerative disorders that includes amyotrophic lateral sclerosis frontotemporal lobar degeneration. It is unclear how FUS cause disease human patients. In this work, we generated novel transgenic mouse models expressing low levels mutant FUS, both which recapitulate aspects the diseases. We found profound difference underlying mechanisms by mutation...
NMNAT2 is an NAD + -synthesizing enzyme with essential axon maintenance role in primary culture neurons. We have generated Nmnat2 gene trap mouse to examine the of vivo . Homozygotes die perinatally a severe peripheral nerve/axon defect and truncated axons optic nerve other CNS regions. The cause appears be limited extension, rather than dying-back degeneration existing axons, which was previously proposed for NMNAT2-deficient Blad mutant mouse. Neurite outgrowth both PNS neuronal cultures...
Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL) and Niemann-Pick type C (NPC), is implicated in Alzheimer's disease (AD) frontotemporal lobar degeneration (FTLD-TDP) with progranulin (PGRN) deficiency. Here, we show that PGRN involved homeostasis lipid metabolism. deficiency alters lysosome abundance morphology mouse neurons. Using an unbiased lipidomic approach, found brain composition humans mice shows disease-specific...
Frontotemporal dementia (FTD) is the most common cause of in people under 60 yr age and pathologically associated with mislocalization TAR DNA/RNA binding protein 43 (TDP-43) approximately half cases (FLTD-TDP). Mutations gene encoding progranulin (GRN), which lead to reduced levels, are a significant familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 neurodegeneration. Here, we report retinal thinning early disease phenotype humans GRN mutations that...
Nicastrin is an integral component of the high molecular weight presenilin complexes that control proteolytic processing amyloid precursor protein and Notch. We report here nicastrin most probably a type 1 transmembrane glycoprotein expressed at moderate levels in brain cultured neurons. Immunofluorescence studies demonstrate localized endoplasmic reticulum, Golgi, discrete population vesicles. Glycosidase analyses reveal endogenous undergoes conventional, trafficking-dependent maturation...
Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, a recent study has suggested locus chromosome 12.To confirm or refute the existence of familial AD 12 in an independent sample cases.Retrospective cohort study. DNA data for 6 genetic markers were evaluated using parametric lod score nonparametric linkage methods heterogeneity tests. The latter include admixture test homogeneity total group families predivided stratified by presence absence...
Two genes encode Fc gamma RIII (CD16), a low affinity FcR for IgG. CD16-I is expressed as phosphatidylinositol glycan-anchored membrane glycoprotein on neutrophils, whereas CD16-II transmembrane-linked NK cells. Membrane anchoring determined by codon 203. Site-directed mutation of 203 and transient expression these cDNA in COS-7 cells indicated that Phe, Ile, Leu, Val permit transmembrane expression, Ser, Thr, Tyr, Asn, Gly, Ala, Asp Lys enable phosphatidylinositol-glycan attachment. Thus,...