Search results for: Michael R. Sierks

Items from 1 to 20 out of 30 results

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Bispecific Antibody Fragment Targeting APP and Inducing α-Site Cleavage Restores Neuronal Health in an Alzheimer’s Mouse Model

Ping He, Wei Xin, Philip Schulz, Michael R. Sierks

Molecular Neurobiology > 2019 > 56 > 11 > 7420-7432

The amyloid β (Aβ) peptide, correlated with development of Alzheimer’s disease (AD), is produced by sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Alternative proteolytic cleavage of APP by α-secretase prevents formation of Aβ peptide and produces a neuroprotective protein, a soluble fragment of APPα (sAPPα). We previously generated a single-chain variable...

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APP/Aβ structural diversity and Alzheimer's disease pathogenesis

Alex E. Roher, Tyler A. Kokjohn, Steven G. Clarke, Michael R. Sierks, more

Neurochemistry International > 2017 > 110 > C > 1-13

The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1–40 and 1–42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that...

article

TDP-43 protein variants as biomarkers in amyotrophic lateral sclerosis

Stephanie M. Williams, Galam Khan, Brent T. Harris, John Ravits, more

BMC Neuroscience > 2017 > 18 > 1 > 1-12

Background TDP-43 aggregates accumulate in individuals affected by amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, representing potential diagnostic and therapeutic targets. Using an atomic force microscopy based biopanning protocol developed in our lab, we previously isolated 23 TDP-43 reactive antibody fragments with preference for human ALS brain tissue relative to frontotemporal...

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Oligomeric α‐synuclein and β‐amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases

Stephanie M. Williams, Philip Schulz, Michael R. Sierks, Paul Bolam

European Journal of Neuroscience > 43 > 1 > 3 - 16

Oligomeric forms of α‐synuclein and β‐amyloid are toxic protein variants that are thought to contribute to the onset and progression of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. The detection of toxic variants in human cerebrospinal fluid (CSF) and blood has great promise for facilitating early and accurate diagnoses of these devastating diseases. Two hurdles that have impeded...

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A novel nicotinic mechanism underlies β-amyloid-induced neurotoxicity

Qiang Liu, Xitao Xie, Sharareh Emadi, Michael R. Sierks, more

Neuropharmacology > 2015 > 97 > Complete > 457-463

Loss of basal forebrain cholinergic neurons (BFCN) correlates with cognitive deficits in Alzheimer disease (AD). Our recent evidence suggests that chronic exposure to Aβ up-regulated neuronal α7-nAChRs and increased neuronal excitability in cultured hippocampal neurons. However, the impact of the up-regulated α7-nAChRs on Aβ-induced neurotoxicity remains unclear. In this study, we investigated the...

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Isolation and characterization of antibody fragments selective for toxic oligomeric tau

Huilai Tian, Eliot Davidowitz, Patricia Lopez, Ping He, more

Neurobiology of Aging > 2015 > 36 > 3 > 1342-1355

Oligomeric tau species are important in the onset and progression of Alzheimer's disease (AD), as they are neurotoxic and can propagate tau-tangle pathology. Therefore, reagents that selectively recognize different key morphologies of tau are needed to help define the role of tau in AD and related diseases. We utilized a biopanning protocol that combines the binding diversity of phage-displayed antibody...

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Nanobody specific for oligomeric beta-amyloid stabilizes nontoxic form

Srinath Kasturirangan, Lin Li, Sharareh Emadi, Shanta Boddapati, more

Neurobiology of Aging > 2012 > 33 > 7 > 1320-1328

While accumulation and deposition of beta amyloid (Aβ) is a primary pathological feature of Alzheimer's disease (AD), increasing evidence has implicated small, soluble oligomeric aggregates of Aβ as the neurotoxic species in AD. Reagents that specifically recognize oligomeric morphologies of Aβ have potential diagnostic and therapeutic value. Using a novel biopanning technique that combines phage...

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Inhibiting β-Secretase Activity in Alzheimer's Disease Cell Models with Single-Chain Antibodies Specifically Targeting APP

Shanta Boddapati, Yona Levites, Michael R. Sierks

Journal of Molecular Biology > 2011 > 405 > 2 > 436-447

The Amyloid-β (Aβ) peptide is produced from the amyloid precursor protein (APP) by sequential proteolytic cleavage of APP first by β-secretase and then by γ-secretase. β-Site APP cleaving enzyme-1 (BACE-1) is the predominant enzyme involved in β-secretase processing of APP and is a primary therapeutic target for treatment of Alzheimer's disease. While inhibiting BACE-1 activity has obvious therapeutic...

article

Engineered Proteolytic Nanobodies Reduce Aβ Burden and Ameliorate Aβ-Induced Cytotoxicity

Srinath Kasturirangan, Shanta Boddapati, Michael R. Sierks

Biochemistry > 2010 > 49 > 21 > 4501 - 4508

article

Cyclodextrins promote protein aggregation posing risks for therapeutic applications

Min S. Wang, Shanta Boddapati, Michael R. Sierks

Biochemical and Biophysical Research Communications > 2009 > 386 > 3 > 526-531

The presence of neurofibrillary tangles (NFTs) is a hallmark feature of various neurodegenerative disorders including Alzheimer’s (AD) and Niemann-Pick type C (NPC) diseases. NFTs have been correlated with elevated cholesterol levels and a cholesterol-scavenging compound, cyclodextrin, effectively modulates and traffics cholesterol from cell bodies in NPC disease models. Cyclodextrins are also used...

article

Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells

Bin Yuan, Michael R. Sierks

Neuroscience Letters > 2009 > 459 > 1 > 16-18

Intracellular clearance of toxic protein aggregates represents a promising therapeutic approach to treat protein-misfolding diseases such as Parkinson's and Huntington's diseases. Intracelluarly expressed antibody fragments or intrabodies can be used to bind specific intracellular targets. Addition of a non-traditional secretion signal sequence enables the intrabody to first bind its target inside...

article

Characterizing Antibody Specificity to Different Protein Morphologies by AFM

Min S. Wang, Andleeb Zameer, Sharareh Emadi, Michael R. Sierks

Langmuir > 2009 > 25 > 2 > 912 - 918

article

Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells

Andleeb Zameer, Srinath Kasturirangan, Sharareh Emadi, Sridevi V. Nimmagadda, more

Journal of Molecular Biology > 2008 > 384 > 4 > 917-928

The Amyloid-β (Aβ) peptide is a major component of the amyloid plaques associated with Alzheimer's disease (AD). Recent studies suggest that the most toxic forms of Aβ are small, soluble oligomeric aggregates. Here, we report the isolation and characterization of a single-chain variable domain (scFv) antibody isolated against oligomeric Aβ using a protocol developed in our laboratory that combines...

article

P1-496: Acidic pH effects on beta-amyloid aggregation and cytotoxicity

Min S. Wang, Michael R. Sierks

Alzheimer's & Dementia: The Journal of the Alzheimer's Association > 2008 > 4 > 4 Supplement > T365

article

P2-417: Beta-site specific ScFv's to decrease Abeta generation and toxicity in Alzheimer's disease

Shanta P. Boddapati, Michael R. Sierks

Alzheimer's & Dementia: The Journal of the Alzheimer's Association > 2008 > 4 > 4 Supplement > T495-T496

article

Characterization of an antibody scFv that recognizes fibrillar insulin and β-amyloid using atomic force microscopy

Warren D. Marcus, Hongda Wang, Stuart M. Lindsay, Michael R. Sierks

Nanomedicine: Nanotechnology, Biology, and Medicine > 2008 > 4 > 1 > 1-7

Fibrillar amyloid is the hallmark feature of many protein aggregation diseases, such as Alzheimer's and Parkinson's diseases. A monoclonal single-chain variable fragment (scFv) targeting insulin fibrils was isolated using phage display technology and an atomic force microscopy (AFM) mica substrate. Specific targeting of the scFv to insulin fibrils but not monomers or other small oligomeric forms,...

article

Anti-oligomeric single chain variable domain antibody differentially affects huntingtin and α-synuclein aggregates

Brent L. Nannenga, Andleeb Zameer, Michael R. Sierks

FEBS Letters > 2008 > 582 > 4 > 517-522

Huntington’s and Parkinson’s diseases are both neurodegenerative disorders caused at least in part by misfolding and aggregation of huntingtin (htt) and α-synuclein, respectively. Here we use a single chain antibody fragment (scFv) isolated against oligomeric α-synuclein to probe similarities and differences between the aggregation and toxic mechanisms of htt and α-synuclein. When incubated with htt,...

article

Single-molecule selection and recovery of structure-specific antibodies using atomic force microscopy

Luda S. Shlyakhtenko, Bin Yuan, Sharareh Emadi, Yuri L. Lyubchenko, more

Nanomedicine: Nanotechnology, Biology, and Medicine > 2007 > 3 > 3 > 192-197

Protein misfolding and aggregation are a common thread in numerous diseases including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, diabetes, and prion-related diseases. Elucidation of the role played by the various protein forms in these diseases requires reagents that can target specific protein forms. Here we present a method to isolate antibodies that bind to a specific...

article

Isolation of a Human Single Chain Antibody Fragment Against Oligomeric α-Synuclein that Inhibits Aggregation and Prevents α-Synuclein-induced Toxicity

Sharareh Emadi, Hedieh Barkhordarian, Min S. Wang, Philip Schulz, more

Journal of Molecular Biology > 2007 > 368 > 4 > 1132-1144

Protein misfolding and aggregation are pathological aspects of numerous neurodegenerative diseases. Aggregates of α-synuclein are major components of the Lewy bodies and Lewy neurites associated with Parkinson's Disease (PD). A natively unfolded protein, α-synuclein can adopt different aggregated morphologies, including oligomers, protofibrils and fibrils. The small oligomeric aggregates have been...

article

Single Chain Fv Antibodies against the 25−35 Aβ Fragment Inhibit Aggregation and Toxicity of Aβ42 ^†

Andleeb Zameer, Philip Schulz, Min S. Wang, Michael R. Sierks

Biochemistry > 2006 > 45 > 38 > 11532 - 11539

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Search results for: Michael R. Sierks

Bispecific Antibody Fragment Targeting APP and Inducing α-Site Cleavage Restores Neuronal Health in an Alzheimer’s Mouse Model

APP/Aβ structural diversity and Alzheimer's disease pathogenesis

TDP-43 protein variants as biomarkers in amyotrophic lateral sclerosis

Oligomeric α‐synuclein and β‐amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases

A novel nicotinic mechanism underlies β-amyloid-induced neurotoxicity

Isolation and characterization of antibody fragments selective for toxic oligomeric tau

Nanobody specific for oligomeric beta-amyloid stabilizes nontoxic form

Inhibiting β-Secretase Activity in Alzheimer's Disease Cell Models with Single-Chain Antibodies Specifically Targeting APP

Engineered Proteolytic Nanobodies Reduce Aβ Burden and Ameliorate Aβ-Induced Cytotoxicity

Cyclodextrins promote protein aggregation posing risks for therapeutic applications

Intracellular targeting and clearance of oligomeric alpha-synuclein alleviates toxicity in mammalian cells

Characterizing Antibody Specificity to Different Protein Morphologies by AFM

Anti-oligomeric Aβ Single-chain Variable Domain Antibody Blocks Aβ-induced Toxicity Against Human Neuroblastoma Cells

P1-496: Acidic pH effects on beta-amyloid aggregation and cytotoxicity

P2-417: Beta-site specific ScFv's to decrease Abeta generation and toxicity in Alzheimer's disease

Characterization of an antibody scFv that recognizes fibrillar insulin and β-amyloid using atomic force microscopy

Anti-oligomeric single chain variable domain antibody differentially affects huntingtin and α-synuclein aggregates

Single-molecule selection and recovery of structure-specific antibodies using atomic force microscopy

Isolation of a Human Single Chain Antibody Fragment Against Oligomeric α-Synuclein that Inhibits Aggregation and Prevents α-Synuclein-induced Toxicity

Single Chain Fv Antibodies against the 25−35 Aβ Fragment Inhibit Aggregation and Toxicity of Aβ42 ^†

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