A5027047896- Alzheimer's disease research and treatments
- Enzyme Production and Characterization
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Prion Diseases and Protein Misfolding
- Parkinson's Disease Mechanisms and Treatments
- Carbohydrate Chemistry and Synthesis
- Advanced Biosensing Techniques and Applications
- Neurological disorders and treatments
- Protein purification and stability
- Microbial Metabolites in Food Biotechnology
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Enzyme Catalysis and Immobilization
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Cholinesterase and Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- Phytase and its Applications
- Computational Drug Discovery Methods
- Force Microscopy Techniques and Applications
- Bacteriophages and microbial interactions
- Advanced biosensing and bioanalysis techniques
Arizona State University
2015-2024
University of California, San Francisco
2018
San Francisco VA Medical Center
2018
Northern California Institute for Research and Education
2018
Rockefeller University
2016
In-Q-Tel
2011
Icahn School of Medicine at Mount Sinai
2008
Maricopa Medical Center
2005
Purdue University West Lafayette
2005
New York State Department of Health
2004
Abstract Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the etiopathogenesis is that oAβ initiates pathology slowly spreads throughout medial temporal cortex neocortices independently Aβ, eventually leading memory loss. Here we show brief exposure extracellular recombinant human oligomers (oTau), but not monomers, produces an impairment long-term potentiation (LTP)...
Research Article| November 15 1989 Sequence homology between putative raw-starch binding domains from different starch-degrading enzymes B Svensson; Svensson *Department of Chemistry, Carlsberg Laboratory, Gamle Vej 10, DK-2500 Copenhagen Valby, Denmark Search for other works by this author on: This Site PubMed Google Scholar H Jespersen; Jespersen M R Sierks; Sierks E A MacGregor †Department University Manitoba, Winnipeg, Canada R3T 2N2 Biochem J (1989) 264 (1): 309–311....
Structure-prediction and hydrophobic-cluster analysis of several starch hydrolases related enzymes indicated the organization eleven domain types. Most possess a catalytic (beta/alpha)8-barrel smaller C-terminal as seen in crystal structures alpha-amylase cyclodextrin glucanotransferase. Some also have starch-granule-binding domain. Enzymes breaking or forming endo-alpha-1,6 linkages contain domains N-terminal to (beta/alpha)8-barrel.
Abstract Background Overexpression and abnormal accumulation of aggregated α-synuclein (αS) have been linked to Parkinson's disease (PD) other synucleinopathies. αS can misfold adopt a variety morphologies but recent studies implicate oligomeric forms as the most cytotoxic species. Both genetic mutations chronic exposure neurotoxins increase aggregation intracellular reactive oxygen species (ROS), leading mitochondrial dysfunction oxidative damage in PD cell models. Results Here we show that...
Nicotinic acetylcholine receptors (nAChRs) containing α7 subunits are thought to assemble as homomers. α7-nAChR function has been implicated in learning and memory, alterations of have found patients with Alzheimer's disease (AD). Here we report findings consistent a novel, naturally occurring nAChR subtype rodent, basal forebrain cholinergic neurons. In these cells, coexpressed, colocalize, coassemble β2 subunit(s). Compared homomeric α7-nAChRs from ventral tegmental area neurons,...
Significance Release of oligomeric/fibrillar α-synuclein (αSyn) from damaged neurons contributes to neuronal cell death in Parkinson’s disease and other neurodegenerative disorders part via microglial activation. Here, we show that αSyn activates the NLRP3 inflammasome human induced pluripotent stem (hiPSC)-derived microglia (hiMG) dual stimulation involving TLR2 engagement mitochondrial damage. Oligomerized amyloid-β peptide (Aβ), as found Alzheimer’s brains, exacerbates this...
Replacing the anomeric C atom of 2-deoxy-O-glucose with an N and ring O a leads to 1, most potent β-glycosidase inhibitor known date. This synthetic monosaccharide derivative also inhibits other glucosidases better than naturally occurring sugar derivatives in which only is exchanged for atom.
We examined the effects of co-incubating nine different Abeta peptide fragments with full-length Abeta1-40 (Abeta40) on protein aggregation. Six enhanced aggregation Abeta40 (Abeta1-28, 12-28, 17-28, 10-20, 25-35 and 17-40), while three others did not (Abeta1-11, 1-16, 20-29). All peptides that contained either residues 17-20 or 30-35, indicating importance these regions for promoting Abeta. Abeta25-35 in particular increased both rate extent considerably as indicated by fluorescence...
beta-Amyloid peptide (Abeta) is the major constituent of senile plaques, key pathological feature Alzheimer's disease. Abeta physiologically produced as a soluble form, but aggregation monomers into oligomers/fibrils causes neurotoxic change peptide. In nature, many microorganisms accumulate small molecule chaperones (SMCs) under stressful conditions to prevent misfolding/denaturation proteins and maintain their stability. Hence, it conceivable that SMCs such ectoine hydroxyectoine could be...
Journal Article Catalytic mechanism of fungal glucoamylase as defined by mutagenesis Asp176, Glu179 and Glu180 in the enzyme from Aspergillus awamori Get access Michael R. Sierks, Sierks 1Departments Chemical EngineeringAmes, IA,50011, USA2Department Chemistry, Carlsberg LaboratoryDK-2500 Copenhagen Valby, Denmark Search for other works this author on: Oxford Academic PubMed Google Scholar Clark Ford, Ford 3Departments Genetics, Iowa state UniversityAmes, USA Peter J. Reilly, Reilly Birte...
A number of hypotheses regarding how anti-Abeta antibodies alter amyloid deposition have been postulated, yet there is no consensus as to Abeta immunotherapy works. We examined the in vivo binding properties, pharmacokinetics, brain penetrance, and alterations levels after a single peripheral dose both wild-type (WT) young non-Abeta depositing APP BRI-Abeta42 mice. The rapid rise plasma observed antibody (Ab) administration attributable prolongation half-life bound Ab. Only miniscule...
Neuropathologic and genetics studies as well transgenic animal models have provided strong evidence linking misfolding aggregation of α-synuclein to the progression Parkinson disease (PD) other related disorders. A growing body implicates various oligomeric forms toxic species responsible for neurodegeneration neuronal cell death. Although numerous different been identified in vitro, it is not known which are involved PD or how, when, where contribute PD. Reagents that can interact with...
In Alzheimer’s disease (AD), tau aggregates into fibrils and higher order neurofibrillary tangles, a key histopathological feature of AD. However, soluble oligomeric species may play more critical role in AD progression since these correlate better with neuronal loss cognitive dysfunction. Recent studies show that extracellular can inhibit memory formation synaptic function also transmit pathology to neighboring neurons. the specific forms involved toxicity are still unknown. Here, we used...
Journal Article CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease Get access Michael R. Sierks, Sierks Department Chemical Engineering, Box 876106, Arizona State University, Tempe, AZ 85287. Fax: 480-727-9321; Tel: 480-965-2828 E-mail: sierks@asu.edu Search other works by this author on: Oxford Academic Google Scholar Gaurav Chatterjee, Chatterjee Electrical, Computer Energy 85287 Claire McGraw, McGraw Srinath Kasturirangan, Kasturirangan...
Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed Fc receptors. For this study, we investigated an scFV directed oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B...
Abstract Oligomeric forms of α‐synuclein and β‐amyloid are toxic protein variants that thought to contribute the onset progression Parkinson's disease ( PD ) Alzheimer's AD ), respectively. The detection in human cerebrospinal fluid CSF blood has great promise for facilitating early accurate diagnoses these devastating diseases. Two hurdles have impeded use as biomarkers availability reagents can bind different a sensitive assay detect their very low concentrations. We previously isolated...
alpha-Synuclein (alpha-syn) has been identified as the major component of Lewy bodies that characterize neurodegenerative synucleinopathies, including Parkinson's disease. Overexpression alpha-syn, and prefibrillar alpha-syn oligomers, implicated in these pathologies; therefore, prevention prefibril accumulation, inhibition other aberrant effects overexpressed could provide novel treatments. Here, we have selected a human single-chan Fv (scFv) antibody, D10, binds monomeric wild-type...
β-Amyloid (Aβ) is a major pathological determinant of Alzheimer's disease (AD). Both active and passive immunization studies have shown that antibodies against Aβ are effective in decreasing cerebral levels, reducing accumulation, attenuating cognitive deficits animal models AD. However, the therapeutic potential these human AD patients limited because adverse inflammatory reactions hemorrhaging associated with treatments. Here we show single chain variable fragments (scFv's) represent an...
The α-synuclein protein has been strongly correlated with Parkinson's disease (PD) and is a major component of the hallmark Lewy body aggregates associated PD. Two different mutations in gene as well increased dosage wild-type all associate early onset cases PD; transgenic animal models overexpressing develop PD symptoms. α-Synuclein, natively unfolded protein, can adopt number folded conformations including β-sheet form that facilitates formation numerous aggregated morphologies, long...
Sensing of three cytokines related to chronic wound healing, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), with detection limits at or below 1 ng/mL in buffered saline solution spiked cell culture medium (CCM) has been achieved. Fiber-optic surface plasmon resonance (SPR) sensors are coated an antibody binding layer antibodies specific the cytokine interest covalently attached this layer. To achieve such a complex as CCM, total protein content 4 mg/mL, use...