Amyloid β-Protein Assembly and Alzheimer Disease

Roychaudhuri, Robin; Yang, Min; Hoshi, Minako; Teplow, David B.

doi:10.1074/jbc.r800036200

Cited by 576 publications

(602 citation statements)

References 53 publications

(74 reference statements)

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“…Structural conversion is a well-known phenomenon in prion pathology where the misfolded scrapie form PrP sc can convert native PrP c into scrapie form 34 . Seeding of amyloid fibrils with amyloid protein is often used to generate homogenous fibril species 35 or eliminate the nucleation step to form amyloid oligomers 36,37 . Recently, oligomer cross-seeding of Ab and asynuclein to induce toxic t-oligomers was demonstrated 38 .…”

Section: Resultsmentioning

confidence: 99%

“…The phenomenon has been discovered in many of those pathogenic proteins such as Ab and t in AD, a-synuclein in Parkinson's disease and prions in prion diseases. Ab in AD progressively aggregates into cross-b amyloid fibrils through a nucleationdependent polymerization pathway 36 . The intermediate prefibrillar Ab oligomers have been found to correlate best with cognitive impairment and synaptic dysfunction 11 .…”

Section: Discussionmentioning

confidence: 99%

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Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients

et al. 2014

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Proteinaceous inclusions are common hallmarks of many neurodegenerative diseases. TDP-43 proteinopathies, consisting of several neurodegenerative diseases, including frontotemporal lobar dementia (FTLD) and amyotrophic lateral sclerosis (ALS), are characterized by inclusion bodies formed by polyubiquitinated and hyperphosphorylated full-length and truncated TDP-43. The structural properties of TDP-43 aggregates and their relationship to pathogenesis are still ambiguous. Here we demonstrate that the recombinant full-length human TDP-43 forms structurally stable, spherical oligomers that share common epitopes with an anti-amyloid oligomer-specific antibody. The TDP-43 oligomers are stable, have exposed hydrophobic surfaces, exhibit reduced DNA binding capability and are neurotoxic in vitro and in vivo. Moreover, TDP-43 oligomers are capable of cross-seeding Alzheimer's amyloid-b to form amyloid oligomers, demonstrating interconvertibility between the amyloid species. Such oligomers are present in the forebrain of transgenic TDP-43 mice and FTLD-TDP patients. Our results suggest that aside from filamentous aggregates, TDP-43 oligomers may play a role in TDP-43 pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients

et al. 2014

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“…In contrast to fibril formation which shows a typical lag phase or nucleation, the assembly of spherical oligomers and other prefibrillar forms has been reported to occur in several proteins without a definite lag phase, leading to the formation of spherical particles or shorter and thinner fibrils than mature amyloid fibrils (Modler et al 2003;Hurshman et al 2004;Gosal et al 2005;Carrotta et al 2005;Bader et al 2006;Roychaudhuri et al 2009;Bhak et al 2009). The molecular mechanisms underlying the lag phase-and nonlag phase-dependent kinetic routes and morphological features of protein aggregation are not fully understood (Uversky 2010;Eichner and Radford 2011a).…”

Section: Introductionmentioning

confidence: 99%

Application and use of differential scanning calorimetry in studies of thermal fluctuation associated with amyloid fibril formation

Sasahara

Goto

2012

Biophys Rev

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The aggregation of proteins into amyloid fibrils is a topic that has attracted great interest because the process is associated with the pathology of numerous human diseases. Despite considerable progress in the elucidation of the structure of amyloid fibrils and the kinetic mechanism of their formation, knowledge on the thermodynamic aspects underlying the formation and stability of amyloid fibrils is limited. In this review, we summarize recent calorimetric studies of amyloid fibril formation, with the goal of obtaining a better understanding of the causal factors that thermally induce proteins to aggregate into amyloid fibrils. Calorimetric data show that differential scanning calorimetry is a useful technique to study the causative factors that thermally trigger the conversion to the amyloid structure and highlight the physics related to the thermal fluctuation of proteins during this conversion.

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“…Several studies have proved that the amyloid-β (Aβ) peptide, which is derived from the Aβ precursor protein (APP), is responsible for AD [1][2][3]and is supported by hundreds of studies over the past two decades [4][5][6][7][8][9][10][11]. After synthesis from APP, Aβ spontaneously aggregates into β-sheet rich fibrils, resembling those in plaques.…”

Section: Introductionmentioning

confidence: 99%

A Chromatography based interaction analysis of two important biomolecules: neurotoxic Amyloid beta oligomers and human blood plasma proteins

2015

J App Biol Biotech

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A Size exclusion Chromatographic analysis was carried out to study the co-elution pattern as well as the molecular interaction between neurotoxic Amyloid beta oligomers and human blood plasma proteins. Four different types of Chromatographic columns like Sephacryl S-100 HR, Superose 12HR 10/30, Superdex 75 HR 10/300 and Superdex 200 HR10/300 used for analysis and among these columns, Superdex 200 HR 10/300 shown to be the most convenient column with better resolution where 20 mM sodium phosphate, pH 7.4; 150 mM sodium chloride proved as best working buffer at 0.5 ml/min flow rate. Co-elution study of mixture of amyloid β oligomers and human plasma serum showed weak molecular interactions with blood plasma proteins but no strong interaction could be observed.

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Amyloid β-Protein Assembly and Alzheimer Disease

Cited by 576 publications

References 53 publications

Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients

Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients

Application and use of differential scanning calorimetry in studies of thermal fluctuation associated with amyloid fibril formation

A Chromatography based interaction analysis of two important biomolecules: neurotoxic Amyloid beta oligomers and human blood plasma proteins

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