Mohsen Nemat-Gorgani

Mohsen Nemat-Gorgani
Stanford University | SU

About

71
Publications
8,312
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1,688
Citations
Citations since 2016
8 Research Items
701 Citations
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100

Publications

Publications (71)
Article
Alpha-synuclein (α-syn) aggregation and mitochondrial dysfunction are considered as two of the main factors associated with Parkinson's disease (PD). In the present investigation, the effectiveness of the amyloid fibrils obtained from α-syn with those of hen egg white lysozyme (HEWL), as disease-related and-unrelated proteins, to damage rat brain a...
Article
Full-text available
There are many reports demonstrating that various derivatives of carbon nanoparticles are effective inhibitors of protein aggregation. As surface structural features of nanoparticles play a key role on modulating amyloid fibrillation process, in the present in vitro study, bovine insulin and hen egg white lysozyme (HEWL) were selected as two model...
Article
Full-text available
Among therapeutic approaches for amyloid-related diseases, attention has recently turned to the use of natural products as effective anti-aggregation compounds. Although a wealth of in vitro and in vivo evidence indicates some common inhibitory activity of these compounds, they don’t generally suggest the same mechanism of action. Here, we show tha...
Data
Figure A. ThT fluorescence intensity of HEWL (50 μM) in the presence of various concentrations of taxifolin (0–200 μM). Samples were incubated in 50 mM glycine (pH 2.2) at 57°C for 7 days. Figure B. AFM images of HEWL (50 μM) incubated alone in 50 mM glycine buffer (pH 2.2) at 57°C for 7 days. Arrows from left to right indicate worm-like fibrils, r...
Article
Peptides and proteins convert from their native states to amyloid fibrillar aggregates in a number of pathological conditions. Characterizing these species could provide useful information on their pathogenicity and the key factors involved in their generation. In this study, we have observed the ability of the model protein apo-bovine carbonic anh...
Article
An increasing number of studies conducted under in vitro and in vivo conditions, have concluded that polyphenols, compounds frequently occurring in many herbs with antioxidant properties, prevent and reverse amyloid fibril formation. However, the mechanisms by which these natural products modulate the protein aggregation process are poorly understo...
Article
Full-text available
Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of "generic" compounds is implicitly acknowledged. Curcumin seems to be one of these compounds, possessing key s...
Article
Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder selectively affecting motor neurons; 90% of the total cases are sporadic, but 2% are associated with mutations in the gene coding for copper-zinc superoxide dismutase (SOD1). The causes of motor neuron death in ALS are poorly understood in general, but for SOD1-li...
Article
Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, although the relative degree of this functional impairment and the mechanism of selective vulnerability in different regions of the brain related to various neurological diseases are not completely understood. In a recent study, we reported on brain mitochondrial mem...
Article
Full-text available
Chemical modification or mutation of proteins may bring about significant changes in the net charge or surface hydrophobicity of a protein structure. Such events may be of major physiological significance and may provide important insights into the genetics of amyloid diseases. In the present study, fibrillation potential of native and chemically-m...
Article
Detailed knowledge of conformation and dynamics of native, intermediate and unfolded states of a protein is essential in searching for effective small molecules to prevent its aggregation. In a recent study we have demonstrated how allosteric effectors may influence protein-protein interactions at high temperatures using glutamate dehydrogenase (GD...
Article
Amyloids are protein fibrils of nanometer size resulting from protein self-assembly. They have been shown to be associated with a wide variety of diseases such as Alzheimer's and Parkinson's and may contribute to various other pathological conditions, known as amyloidoses. Insulin is prone to form amyloid fibrils under slightly destabilizing condit...
Data
Database reporting a list of peptides or proteins forming extracellular amyloid deposits or intracelullar inclusions with amyloid-like characteristics in human diseases. The names of the proteins, their sizes, their associated pathologies and references are reported. (DOC)
Data
Database of peptides or proteins forming intracellular or extracellular non-amyloid deposits in human diseases. The names of the proteins, their sizes, their associated pathologies and references are reported. (DOC)
Article
Full-text available
The assembly of soluble proteins into ordered fibrillar aggregates with cross-β structure is an essential event of many human diseases. The polypeptides undergoing aggregation are generally small in size. To explore if the small size is a primary determinant for the formation of amyloids under pathological conditions we have created two databases o...
Article
Formation of toxic amyloid structures is believed to be associated with various late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The fact that many proteins in addition to those that are associated with clinical conditions have the potential to form amyloid fibrils in vitro provides opportunities for studying the...
Article
Full-text available
Protein aggregates, whether amorphous or structured (amyloid), have attracted much attention in recent years and despite extensive efforts, the mechanism of their formation is poorly understood. While “natural” aggregation (polymerization) of monomers could improve the biological function of some proteins, it is usually the darker side of this phen...
Article
Studies on the aggregation of mutant proteins have provided new insights into the genetics of amyloid diseases and the role of the net charge of the protein on the rate, extent, and type of aggregate formation. In the present work, hen egg white lysozyme (HEWL) was employed as the model protein. Acetylation and (separately) citraconylation were emp...
Article
Full-text available
Traditionally, expensive and time consuming techniques such as mass spectrometry and Western Blotting have been used for characterization of protein-protein interactions. In this paper, we describe the design, fabrication, and testing of a rapid and inexpensive sensor, involving the use of microelectrodes in a microchannel, which can be used for re...
Article
Full-text available
Current methods used for analyzing biomarkers involve expensive and time consuming techniques like the Sandwich ELISA which require lengthy incubation times, high reagent costs, and bulky optical equipment. We have developed a technique involving the use of a micro-channel with integrated electrodes, functionalized with receptors specific to target...
Article
Disease diagnosis at an early stage requires the availability of inexpensive platforms which can accurately and rapidly analyze a wide panel of biomarkers, genomic biomarkers in particular. Genetic biomarkers are typically detected through recognition of DNA hybridization events, which is typically performed using DNA microarrays, requiring overnig...
Article
Full-text available
Protein aggregation is of crucial importance in a wide variety of situations. High temperatures, combined with other denaturing conditions, have been used very extensively to decipher some of the fundamentals related to formation of amorphous and fibrillar protein aggregates. The present study reports on the dependency of thermal aggregation of bov...
Article
Amyloid fibril formation is widely believed to be a generic property of polypeptide chains. In the present study, α-chymotrypsin, a well-known serine protease has been driven toward these structures by the use of two different conditions involving (I) high temperature, pH 2.5, and (II) low concentration of trifluoroethanol (TFE), pH 2.5. A variety...
Article
We have developed a simple method using a magnetic bar array to anchor nonmagnetic biomolecules for time-lapse analysis and identification. Biomolecules of interest are attached, using linker molecules, to the superparamagnetic beads which are in turn captured at gaps of the magnetic bar array. This micro-array system can be used for various studie...
Article
Amyloid nanofibril formation appears to be a generic property of polypeptide chains. alpha-Chymotrypsin (aCT) was recently driven toward amyloid-like aggregation by the addition of trifluoroethanol (TFE) at intermediate concentrations. In this study we employed a molecular dynamics simulation to investigate the early events in TFE-induced conformat...
Article
Full-text available
Yeast hexokinase has been poorly characterized in regard with its stability. In the present study, various spectroscopic techniques were employed to investigate thermal stability of the monomeric form of yeast hexokinase B (YHB). The enzyme underwent a conformational transition with a T(m) of about 41.9 degrees C. The structural transition proved t...
Article
The present study reports on the retention of conformational flexibility of a model allosteric protein upon immobilization on self-assembled monolayers (SAMs) on gold. Organothiolated SAMs of different compositions were utilized for adsorptive and covalent attachment of bovine liver glutamate dehydrogenase (GDH), a well-characterized allosteric enz...
Article
Full-text available
Studies on HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical significance. In the present study, the expression of HLA-G proteins in the human skin tissue sections of normal and autoimmune pemphigus vulgaris (PV) individuals were investigated using monoclonal antibodies. The antibodies recognized both membrane-b...
Conference Paper
Current microbiological techniques used for multi-analyte detection, necessary for medical diagnostics, involve expensive and time consuming methods based on sandwich immunoassays. Described below is the design, fabrication, and testing of a rapid and inexpensive sensor, involving the use of microelectrodes in a micro-channel, which can be used to...
Article
Full-text available
Pathogenic bacterial cell detection is currently performed using techniques such as culture enrichment and various plating methods, which are expensive and can take up to several days. In this study, we describe the design, fabrication, and testing of a rapid and inexpensive sensor for detection of target cells electrically in real-time. The sensor...
Article
We have recently reported that electrostatic interactions may play a critical role in alcohol-induced aggregation of alpha-chymotrypsin (CT). In the present study, we have investigated the heat-induced aggregation of this protein. Thermal aggregation of CT obeyed a characteristic pattern, with a clear lag phase followed by a sharp rise in turbidity...
Article
Amyloid aggregation of polypeptides is related to a growing number of pathologic states known as amyloid disorders. There is a great deal of interest in developing small molecule inhibitors of the amyloidogenic processes. In the present article, the inhibitory effects of some indole derivatives on amyloid fibrillation of hen egg white lysozyme (HEW...
Article
Naturally occurring polyamines are known to interact with a variety of biomolecules and critically involve in some important physiological processes. They have also been shown to influence protein aggregation in vitro in some cases. The aim of the present study was to investigate how polyamines may influence the structure and thermal stability of a...
Article
The present communication reports on changes in the secondary and tertiary structures of native and apo-yeast alcohol dehydrogenase upon heating at 50 °C, as evident from circular dichroism (CD) studies. The presence of sugars provided significant protection with trehalose being the most effective. Exposure of hydrophobic clusters in the protein mo...
Article
Full-text available
Currently, microbiological techniques such as culture enrichment and various plating techniques are used for detection of pathogens. These expensive and time consuming methods can take several days. Described below is the design, fabrication, and testing of a rapid and inexpensive sensor, involving the use of microelectrodes in a microchannel, whic...
Article
Full-text available
Type I hexokinase (HK-I) constitutes the predominant form of the enzyme in the brain, a major portion of which is associated with the outer mitochondrial membrane involving two sets of binding sites. In addition to the glucose-6-phosphate (G6P)-sensitive site (Type A), the enzyme is bound on a second set of sites (Type B) which are, while insensiti...
Article
It has been recently demonstrated that alpha-chymotrypsin (CT) can be driven toward amyloid aggregation by addition of 2,2,2-trifluoroethanol (TFE), at intermediate concentrations. In the present article, the process of TFE-induced CT aggregation was investigated in more detailed kinetic terms where the effects of medium conditions, such as tempera...
Article
Full-text available
We report on a rapid simulation method for predicting protein orientation on a surface based on electrostatic interactions. New methods for predicting protein immobilization are needed because of the increasing use of biosensors and protein microarrays, two technologies that use protein immobilization onto a solid support, and because the orientati...
Article
Our previous studies indicated that native carbonic anhydrase does not interact with hydrophobic adsorbents and that it acquires this ability upon denaturation. In the present study, an apo form of the enzyme was prepared by removal of zinc and a comparative study was performed on some characteristic features of the apo and native forms by far- and...
Article
Chemical cross-linking of a mesophilic alpha-amylase from Bacillus amyloliquefaciens (BAA) was carried out. Intra-molecular cross-links between lysine residues upon treatment of the enzyme with ethylene glycol bis(succinic acid N-hydroxy succinimide ester) resulted in enhancement of thermostability as indicated by irreversible thermoinactivation ex...
Article
A comparative structure-function study was performed to establish possible roles of carbohydrates in stabilization of glycoproteins, using glucoamylase (GA) as a model system. In addition to kinetic properties, stability toward elevated temperatures, extremes of pH, high salt concentrations together with circular dichroism, intrinsic/extrinsic fluo...
Article
Full-text available
The lysine residues of Bacillus licheniformis alpha-amylase (BLA) were chemically modified using citraconic anhydride or succinic anhydride. Modification caused fundamental changes in the enzymes specificity, as indicated by a dramatic increase in maltosidase and a reduction in amylase activity. These changes in substrate specificity were found to...
Article
An intermediate form of alpha-amylase from Bacillus subtilis was prepared following a previously reported procedure. Stabilization of this protein structure by various additives and its interaction with alkyl-substituted Sepharose 4B (Sepharose-lipid), used to mimic the role of the alkyl chains of the phospholipid bilayer, were investigated. Exposu...
Article
Chemical modification of lysine residues in glucose oxidase was carried out using citraconic anhydride. Modification brought about changes in the kinetic properties of the enzyme as evident by substantial lowering of V(max) and K(m). Enhancement of tryptophan fluorescence was observed with a dramatic change in its pH dependence due to modification....
Article
Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical importance. In the present study, monoclonal antibodies were prepared which recognize different membrane bound and soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic peptide. Use of this peptid...
Article
Glucose oxidase (GOD) is often used in immobilized forms for determination of glucose. To examine the possibility of its adsorption by hydrophobic interactions, palmityl-substituted Sepharose 4B (Sepharoselipid) was employed as an adsorptive matrix. Various conditions were used in tests to improve the limited immobilization of the enzyme observed u...
Article
Our previous studies indicated that native carbonic anhydrase does not interact with hydrophobic adsorbents and that it acquires this ability upon denaturation. It was concluded that hydrophobic sites become available and that catalytically active immobilized preparations may be finally obtained. In the present study, alkyl-substituted Sepharose 4B...
Article
Alkyl-substituted Sepharose 4B prepared by the glycidyl ether method with different degrees of substitution and alkyl chain length, have been used as a non-ionic matrix for immobilization of bacterial luciferases. Exposure of hydrophobic clusters in the protein molecule was confirmed by fluorescence studies using 8-anilino-1-napthalene-sulfonate as...
Article
Full-text available
Triton X-100-substituted Sepharose 4B (Sepharose-TX) was used for adsorptive immobilization of intestinal brush border membrane using lactose-phlorizin hydrolase as a representative membrane enzyme. Limited heating of membrane preparations was found to enhance binding. This enhancement is concluded to be owing to a greater availability of the hydro...
Article
Full-text available
A comparative study was performed regarding the catalytic activity and stability of two related enzymes (thermophilic alcohol dehydrogenase from Thermoanaerobacter brockii and its mesophilic counterpart from yeast) in the presence of a number of miscible and immiscible organic solvents. The study was performed in view of the practical usefulness of...
Article
In the present study, irreversible thermoinactivation of holo- and apo-yeast alcohol dehydrogenase (YADH, EC 1.1.1.1) and protection by sugars (mannitol, sorbitol, sucrose and trehalose) were investigated at 50°C and pH 7.8. The apo-protein was obtained by removing the structural zinc with the catalytic zinc remaining on the enzyme. Thiol group oxi...
Article
A comparative study was performed on the effect of calcium on native and chemically modified forms of mesophilic and thermophilic α-amylases. Circular dichroism (CD) and irreversible thermoinactivation studies were carried out in the absence and presence of 10 mM calcium. From the CD experiments, changes in the tertiary structure of these enzymes,...
Article
The major portion of rat brain hexokinase (HK type I) is bound to the outer membrane of mitochondria and glucose-6-phosphate (G6P) can release the bound enzyme. In an attempt to look at the hydrophobic component of binding, interaction of the enzyme with a purely hydrophobic matrix, palmityl-substituted Sepharose-4B (Sepharose-lipid) was investigat...
Article
Urease was chosen as a model multimeric protein to investigate the utility of reversible denaturation for immobilization to a hydrophobic support. Of the various procedures investigated, acidic denaturation provided the highest degree of immobilization and enzymatic activity with lowering of K m (apparent). Exposure of hydrophobic clusters in the...
Article
Chemical modification of lysine residues in two bacterial α-amylases, a mesophilic enzyme from Bacillus amyloliquefaciens (BAA) and a thermophilic enzyme from Bacillus licheniformis (BLA) was carried out using citraconic anhydride. 13 ± 1 residues in BAA and 10 ± 1 residues in BLA were found modified under defined experimental conditions. Modificat...
Article
A comparative study was performed on limited and extensive proteolysis of mesophilic (from Bacillus amyloliquefaciens [BAA]) and thermophilic (from Bacillus licheniformis [BLA]) α-amylases using trypsin. As expected, the thermophilic enzyme showed greater resistance to digestion by the protease. While the catalytic potential of BLA was enhanced on...
Article
Interaction of type I hexokinase (HK-I) with the mitochondria obtained from the biopsy specimens of normal and tumoral human brain tissues was studied in the present investigation. This effort was undertaken with the aim of exploring possible differences in the mode of association of the enzyme with the outer mitochondrial membrane in the described...
Article
A comparative study was performed on thermal stability of mesophilic and thermophilic α-amylases, and the effects of various denaturing agents, organic solvents, and stabilizers were investigated. As expected, the thermophilic enzyme showed higher resistance toward denaturation in water as its natural medium, but such a difference could not be dete...
Article
Palmityl-substituted sepharose 4B has been used for adsorptive immobilization of heat-denatured carbonic anhydrase. The native form of this enzyme does not show any affinity for binding to this hydrophobic support. However, through the process of denaturation–renaturation performed by heating and subsequent cooling of an enzyme solution in the pres...
Article
1.1. A comparative study on the catalytic and allosteric properties of particulate and soluble forms of ox liver glutamate dehydrogenase has been carried out. The response of the bound enzyme to release by various effectors was investigated.2.2. The particulate enzyme was found to have catalytic activities similar to the free enzyme in contrast to...
Article
To study changes in lipid-protein-interaction and fluidity in mitochondrial and microsomal membranes of brain during development and aging, the Arrhenius plots of marker enzymes for mitochondrial inner and outer membranes as well as those of microsomal membranes were compared at different ages. The enzymes were, β-hydroxybutyrate dehydrogenase (BDH...