Search results for: Anne Messer

Items from 1 to 20 out of 28 results

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Structure of a Single-Chain Fv Bound to the 17 N-Terminal Residues of Huntingtin Provides Insights into Pathogenic Amyloid Formation and Suppression

Erwin De Genst, Dimitri Y. Chirgadze, Fabrice A.C. Klein, David C. Butler, more

Journal of Molecular Biology > 2015 > 427 > 12 > 2166-2178

Huntington's disease is triggered by misfolding of fragments of mutant forms of the huntingtin protein (mHTT) with aberrant polyglutamine expansions. The C4 single-chain Fv antibody (scFv) binds to the first 17 residues of huntingtin [HTT(1-17)] and generates substantial protection against multiple phenotypic pathologies in situ and in vivo. We show in this paper that C4 scFv inhibits amyloid formation...

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Antibodies and protein misfolding: From structural research tools to therapeutic strategies

Erwin De Genst, Anne Messer, Christopher M. Dobson

BBA - Proteins and Proteomics > 2014 > 1844 > 11 > 1907-1919

Protein misfolding disorders, including the neurodegenerative conditions Alzheimer's disease (AD) and Parkinson's disease (PD) represent one of the major medical challenges or our time. The underlying molecular mechanisms that govern protein misfolding and its links with disease are very complex processes, involving the formation of transiently populated but highly toxic molecular species within the...

article

Intrabodies as Neuroprotective Therapeutics

Anne Messer, Shubhada N. Joshi

Neurotherapeutics > 2013 > 10 > 3 > 447-458

The process of misfolding of proteins that can trigger a pathogenic cascade leading to neurodegenerative diseases largely originates intracellularly. It is possible to harness the specificity and affinity of antibodies to counteract either protein misfolding itself, or the aberrant interactions and excess stressors immediately downstream of the primary insult. This review covers the emerging field...

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Engineered antibody therapies to counteract mutant huntingtin and related toxic intracellular proteins

David C. Butler, Julie A. McLear, Anne Messer

Progress in Neurobiology > 2012 > 97 > 2 > 190-204

The engineered antibody approach to Huntington's disease (HD) therapeutics is based on the premise that significantly lowering the levels of the primary misfolded mutant protein will reduce abnormal protein interactions and direct toxic effects of the misfolded huntingtin (HTT). This will in turn reduce the pathologic stress on cells, and normalize intrinsic proteostasis. Intracellular antibodies...

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Nicotinamide improves motor deficits and upregulates PGC-1α and BDNF gene expression in a mouse model of Huntington's disease

Tyisha Hathorn, Abigail Snyder-Keller, Anne Messer

Neurobiology of Disease > 2011 > 41 > 1 > 43-50

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine (polyQ) repeat in exon-1 in the Huntingtin gene (HTT). This results in misfolding and accumulation of the huntingtin (htt) protein, forming nuclear and cytoplasmic inclusions. HD is associated with dysregulation of gene expression as well as mitochondrial dysfunction. We hypothesized...

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Mini-review: Polybrominated diphenyl ether (PBDE) flame retardants as potential autism risk factors

Anne Messer

Physiology & Behavior > 2010 > 100 > 3 > 245-249

Brominated flame retardants, including Polybrominated diphenyl ethers (PBDEs) have been used at increasing levels in home furnishings and electronics over the past 25years. They have also become widespread environmental pollutants. High PBDE levels have been detected in food, household dust, and indoor air, with subsequent appearance in animal and human tissues. This minireview summarizes studies...

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An scFv Intrabody against the Nonamyloid Component of α-Synuclein Reduces Intracellular Aggregation and Toxicity

Sandra M. Lynch, Chun Zhou, Anne Messer

Journal of Molecular Biology > 2008 > 377 > 1 > 136-147

Prevention of abnormal misfolding and aggregation of α synuclein (syn) protein in vulnerable neurons should be viable therapeutic strategies for reducing pathogenesis in Parkinson's disease. The nonamyloid component (NAC) region of α-syn shows strong tendencies to form β-sheet structures, and deletion of this region has been shown to reduce aggregation and toxicity in vitro and in vivo. The binding...

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Molecular characterization of the genetic lesion in Dystonia musculorum (dt-Alb) mice

Dmitry Goryunov, Adijat Adebola, Julius J. Jefferson, Conrad L. Leung, more

Brain Research > 2007 > 1140 > Complete > 179-187

Dystonia musculorum (dt) is an inherited autosomal recessive neuropathy in mice. Homozygous animals display primarily sensory neurodegeneration resulting in a severe loss of coordination. Several dt strains exist, including spontaneous mutants dt-Alb (Albany), dt-J (Jackson Labs), and dt-Frk (Frankel), and a transgene insertion mutant, Tg4. They contain mutations in the gene encoding Bullous Pemphigoid...

article

Fusion Intrabodies as Anti-Huntington Gene Therapy

Julie McLear, Jack Webster, Nikolas Webster, Anne Messer

Molecular Therapy > 2006 > 13 > Supplement 1 > S95-S96

article

The Therapeutic Potential of Intrabodies in Neurologic Disorders

Anne Messer, Julie McLear

BioDrugs > 2006 > 20 > 6 > 327-333

Single-chain Fv and single-domain antibodies retain the binding specificity of full-length antibodies but they can be cloned, selected, engineered, and manipulated as genes. When expressed intracellularly in mammalian cells these intracellular antibodies, or intrabodies, have the potential to alter the folding, interactions, modifications, or subcellular localization of their targets. These reagents...

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Intrabody applications in neurological disorders: progress and future prospects

Todd W. Miller, Anne Messer

Molecular Therapy > 2005 > 12 > 3 > 394-401

Single-chain Fv and single-domain antibodies retain the binding specificity of full-length antibodies, but they can be expressed as single genes in phage or yeast surface-display libraries, thus allowing efficient in vitro selection from a naive human repertoire. Selected genes can then be expressed intracellularly in mammalian cells as intrabodies, with the potential for alteration of the folding,...

article

943. Anti-alpha-Synuclein scFv Study

Chun Zhou, Anne Messer

Molecular Therapy > 2005 > 11 > Supplement 1 > 365

article

A human single-chain Fv intrabody preferentially targets amino-terminal huntingtin fragments in striatal models of Huntington's disease

Todd W. Miller, Chun Zhou, Silvia Gines, Marcy E. MacDonald, more

Neurobiology of Disease > 2005 > 19 > 1-2 > 47-56

Amino-terminal fragments of huntingtin (htt) appear to result from proteolytic processing of the full-length protein in Huntington's disease (HD), and fragments containing pathological expansions of polyglutamine elicit toxicity in model systems. Such fragments are sequestered into insoluble aggregates, which may initially serve a cellular protective mechanism, while soluble fragments and/or oligomers...

article

A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein

Chun Zhou, Sharareh Emadi, Michael R. Sierks, Anne Messer

Molecular Therapy > 2004 > 10 > 6 > 1023-1031

α-Synuclein (α-syn) has been identified as the major component of Lewy bodies that characterize neurodegenerative synucleinopathies, including Parkinson's disease. Overexpression of α-syn, and prefibrillar α-syn oligomers, has been implicated in these pathologies; therefore, prevention of prefibril accumulation, and inhibition of other aberrant effects of overexpressed α-syn, could provide novel treatments...

article

Early postnatal Purkinje cells from staggerer mice undergo aberrant development in vitro with characteristic morphologic and gene expression abnormalities

L. Thomas Shirley, Anne Messer

Developmental Brain Research > 2004 > 152 > 2 > 153-157

The staggerer (sg) mutant mouse shows an early block in Purkinje cell (PC) development due to a truncation of the transcription factor retinoic acid-related orphan receptor alpha (RORα). Cerebellar cultures from neonatal sg mice recapitulate many in vivo postnatal changes in PCs and allow for detailed observation of sequential dendritic outgrowth and gene expression changes. In addition, this in vitro...

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Development of a Human Light Chain Variable Domain (VL) Intracellular Antibody Specific for the Amino Terminus of Huntingtin via Yeast Surface Display

David W. Colby, Payal Garg, Tina Holden, Ginger Chao, more

Journal of Molecular Biology > 2004 > 342 > 3 > 901-912

Intracellular antibodies (intrabodies) provide an attractive means for manipulating intracellular protein function, both for research and potentially for therapy. A challenge in the isolation of effective intrabodies is the ability to find molecules that exhibit sufficient binding affinity and stability when expressed in the reducing environment of the cytoplasm. Here, we have used yeast surface display...

article

Early exploratory behavior abnormalities in R6/1 Huntington's disease transgenic mice

Valerie J. Bolivar, Kevin Manley, Anne Messer

Brain Research > 2004 > 1005 > 1-2 > 29-35

The Huntington's disease (HD) R6/1 transgenic mouse model, containing a human huntington gene exon-1 with approximately 115 CAG repeats, has multiple biochemical and neuroanatomical abnormalities. Overt neurological symptoms have a relatively late onset (15-21 weeks of age). In this paper, we report exploratory behavior abnormalities that appear well before the onset of obvious pathology. The first...

article

Inhibiting Aggregation of α-Synuclein with Human Single Chain Antibody Fragments ^†

Sharareh Emadi, Ruitian Liu, Bin Yuan, Philip Schulz, more

Biochemistry > 2004 > 43 > 10 > 2871 - 2878

article

A single-chain Fv intrabody provides functional protection against the effects of mutant protein in an organotypic slice culture model of Huntington's disease

Robert C. Murphy, Anne Messer

Molecular Brain Research > 2004 > 121 > 1-2 > 141-145

Huntington's disease (HD) is a progressive, hereditary, neurodegenerative disorder caused by an expanded polyglutamine tract in huntingtin protein, leading to misfolding and abnormal protein-protein interactions. Reducing the initial misfolding should lead to decreased pathogenesis. We show that malonate stress increases the number of dead or dying cells when organotypic slice cultures are transduced...

article

DNA vaccination against mutant huntingtin ameliorates the HDR6/2 diabetic phenotype

Todd W. Miller, Thomas L. Shirley, William J. Wolfgang, Xiaowei Kang, more

Molecular Therapy > 2003 > 7 > 5 > 572-579

Immunization against extracellular neurotoxic proteins has shown promise in the treatment of several neurodegenerative disorders. We sought to determine whether immunization against mutant huntingtin, the intracellular protein that causes Huntington's disease (HD), could slow disease progression in the HD mouse model HDR6/2. DNA vaccination was used to present the mutant intracellular antigen to the...

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INFONA - science communication portal

Search results for: Anne Messer

Structure of a Single-Chain Fv Bound to the 17 N-Terminal Residues of Huntingtin Provides Insights into Pathogenic Amyloid Formation and Suppression

Antibodies and protein misfolding: From structural research tools to therapeutic strategies

Intrabodies as Neuroprotective Therapeutics

Engineered antibody therapies to counteract mutant huntingtin and related toxic intracellular proteins

Nicotinamide improves motor deficits and upregulates PGC-1α and BDNF gene expression in a mouse model of Huntington's disease

Mini-review: Polybrominated diphenyl ether (PBDE) flame retardants as potential autism risk factors

An scFv Intrabody against the Nonamyloid Component of α-Synuclein Reduces Intracellular Aggregation and Toxicity

Molecular characterization of the genetic lesion in Dystonia musculorum (dt-Alb) mice

Fusion Intrabodies as Anti-Huntington Gene Therapy

The Therapeutic Potential of Intrabodies in Neurologic Disorders

Intrabody applications in neurological disorders: progress and future prospects

943. Anti-alpha-Synuclein scFv Study

A human single-chain Fv intrabody preferentially targets amino-terminal huntingtin fragments in striatal models of Huntington's disease

A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein

Early postnatal Purkinje cells from staggerer mice undergo aberrant development in vitro with characteristic morphologic and gene expression abnormalities

Development of a Human Light Chain Variable Domain (VL) Intracellular Antibody Specific for the Amino Terminus of Huntingtin via Yeast Surface Display

Early exploratory behavior abnormalities in R6/1 Huntington's disease transgenic mice

Inhibiting Aggregation of α-Synuclein with Human Single Chain Antibody Fragments ^†

A single-chain Fv intrabody provides functional protection against the effects of mutant protein in an organotypic slice culture model of Huntington's disease

DNA vaccination against mutant huntingtin ameliorates the HDR6/2 diabetic phenotype

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