scholarly journals MOMD Analysis of NMR Line Shapes from Aβ-Amyloid Fibrils: A New Tool for Characterizing Molecular Environments in Protein Aggregates

2018 ◽  
Vol 122 (18) ◽  
pp. 4793-4801 ◽  
Author(s):  
Eva Meirovitch ◽  
Zhichun Liang ◽  
Jack H. Freed
Keyword(s):  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Line Shapes ◽  
Aβ Amyloid

scholarly journals Amyloids: The History of Toxicity and Functionality

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 394
Author(s):  
Elmira I. Yakupova ◽  
Liya G. Bobyleva ◽  
Sergey A. Shumeyko ◽  
Ivan M. Vikhlyantsev ◽  
Alexander G. Bobylev
Keyword(s):  
Molecular Structure ◽  
Polypeptide Chain ◽  
Amyloid Plaques ◽  
Protein Aggregates ◽  
Specific Function ◽  
Main Hypothesis ◽  
Amyloid Toxicity ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
History Of

Proteins can perform their specific function due to their molecular structure. Partial or complete unfolding of the polypeptide chain may lead to the misfolding and aggregation of proteins in turn, resulting in the formation of different structures such as amyloid aggregates. Amyloids are rigid protein aggregates with the cross-β structure, resistant to most solvents and proteases. Because of their resistance to proteolysis, amyloid aggregates formed in the organism accumulate in tissues, promoting the development of various diseases called amyloidosis, for instance Alzheimer’s diseases (AD). According to the main hypothesis, it is considered that the cause of AD is the formation and accumulation of amyloid plaques of Aβ. That is why Aβ-amyloid is the most studied representative of amyloids. Therefore, in this review, special attention is paid to the history of Aβ-amyloid toxicity. We note the main problems with anti-amyloid therapy and write about new views on amyloids that can play positive roles in the different organisms including humans.

Dynamics and Fluidity of Amyloid Fibrils:  A Model of Fibrous Protein Aggregates

2002 ◽  
Vol 124 (51) ◽  
pp. 15150-15151 ◽  
Author(s):  
Ami S. Lakdawala ◽  
David M. Morgan ◽  
Dennis C. Liotta ◽  
David G. Lynn ◽  
James P. Snyder
Keyword(s):  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Fibrous Protein

Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells

2018 ◽  
Vol 6 (1) ◽  
pp. 56-67 ◽  
Author(s):  
Baiping Ren ◽  
Yonglan Liu ◽  
Yanxian Zhang ◽  
Mingzhen Zhang ◽  
Yan Sun ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Aβ Amyloid

Tanshinones act as common inhibitors to inhibit the aggregation of both hIAPP and Aβ, disaggregate preformed hIAPP and Aβ amyloid fibrils, and protect cells from hIAPP- and Aβ-induced toxicity.

scholarly journals RETRACTED: Peptide-induced formation of protein aggregates and amyloid fibrils in human and guinea pig αA-crystallins under physiological conditions of temperature and pH

2019 ◽  
Vol 179 ◽  
pp. 193-205 ◽  
Author(s):  
Anbarasu Kumarasamy ◽  
Sivakumar Jeyarajan ◽  
Jonathan Cheon ◽  
Anthony Premceski ◽  
Eric Seidel ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Physiological Conditions

scholarly journals Endo-lysosomal Aβ concentration and pH enable formation of Aβ oligomers that potently induce Tau missorting

2020 ◽  
Author(s):  
Marie P. Schützmann ◽  
Filip Hasecke ◽  
Sarah Bachmann ◽  
Mara Zielinski ◽  
Sebastian Hänsch ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Tau Pathology ◽  
Aβ Oligomers ◽  
Lysosomal Ph ◽  
Amyloid Fibril Formation ◽  
Aβ Amyloid ◽  
Key Factor ◽  
Lysosomal System

AbstractAmyloid-β peptide (Aβ) forms metastable oligomers >50 kD, termed AβOs or protofibrils, that are more effective than Aβ amyloid fibrils at triggering Alzheimer’s disease-related processes such as synaptic dysfunction and Tau pathology, including Tau mislocalization. In neurons, Aβ accumulates in endo-lysosomal vesicles at low pH. Here, we show that the rate of AβO assembly is accelerated 8,000-fold upon pH reduction from extracellular to endo-lysosomal pH, at the expense of amyloid fibril formation. The pH-induced promotion of AβO formation and the high endo-lysosomal Aβ concentration together enable extensive AβO formation of Aβ42 under physiological conditions. Exploiting the enhanced AβO formation of the dimeric Aβ variant dimAβ we furthermore demonstrate targeting of AβOs to dendritic spines, potent induction of Tau missorting, a key factor in tauopathies, and impaired neuronal activity. The results suggest that the endosomal/lysosomal system is a major site for the assembly of pathomechanistically relevant AβOs.

scholarly journals Deletion of Serf2 shifts amyloid conformation in an Aβ amyloid mouse model

2021 ◽  
Author(s):  
E. Stroo ◽  
L. Janssen ◽  
O. Sin ◽  
W. Hogewerf ◽  
M. Koster ◽  
...  
Keyword(s):  
Mouse Model ◽  
Amyloid Fibrils ◽  
Mammalian Brain ◽  
Amyloid Formation ◽  
List Type ◽  
Lung Maturation ◽  
Disease Manifestation ◽  
Aβ Amyloid ◽  
Perinatal Lethality

AbstractNeurodegenerative diseases like Alzheimer, Parkinson and Huntington disease are characterized by aggregation-prone proteins that form amyloid fibrils through a nucleation process. Despite the shared β-sheet structure, recent research has shown that structurally different polymorphs exist within fibrils of the same protein. These polymorphs are associated with varying levels of toxicity and different disease phenotypes. MOAG-4 and its human orthologs SERF1 and SERF2 have previously been shown to modify the nucleation and drive amyloid formation and protein toxicity in vitro and in C. elegans. To further explore these findings, we generated a Serf2 knockout (KO) mouse model and crossed it with the APPPS1 mouse model for Aβ amyloid pathology. Full-body KO of Serf2 resulted in a developmental delay and perinatal lethality due to insufficient lung maturation. Therefore, we proceeded with a brain-specific Serf2 KO, which was found to be viable. We examined the Aβ pathology at 1 and 3 months of age, which is before and after the start of amyloid deposition. We show that SERF2 deficiency does not affect the production and overall Aβ levels. Serf2 KO-APPPS1 mice displayed an increased intracellular Aβ accumulation at 1 month and a higher number of Aβ deposits compared to APPPS1 mice with similar Aβ levels. Moreover, conformation-specific dyes and electron microscopy revealed a difference in the structure and amyloid content of these Aβ deposits. Together, our results reveal that SERF2 causes a structural shift in Aβ aggregation in a mammalian brain. These findings indicate that a single endogenous factor may contribute to amyloid polymorphisms, allowing for new insights into this phenomenon’s contribution to disease manifestation.HighlightsLoss of SERF2 slows embryonic development and causes perinatal lethalitySERF2 affects proliferation in a cell-autonomous fashionBrain-specific Serf2 knockout does not affect viability or Aβ productionBrain deletion of Serf2 shifts the amyloid conformation of Aβ

Is DAPI assay of cellular nucleic acid reliable in the presence of protein aggregates?

2020 ◽  
Vol 56 (89) ◽  
pp. 13844-13847
Author(s):  
Aruna K. Mora ◽  
Sufiyan Khan ◽  
Birija S. Patro ◽  
Sukhendu Nath
Keyword(s):  
Nucleic Acid ◽  
Amyloid Fibrils ◽  
Protein Aggregates

Intracellular amyloid fibrils prevent exclusive staining of nuclei by DAPI.

scholarly journals Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Marius Kollmer ◽  
William Close ◽  
Leonie Funk ◽  
Jay Rasmussen ◽  
Aref Bsoul ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Brain Tissue ◽  
Amyloid Fibrils ◽  
Structural Basis ◽  
Amyloid Angiopathy ◽  
Cryo Electron Microscopy ◽  
Aβ Amyloid ◽  
Cerebral Amyloid ◽  
Aβ Fibrils

Abstract The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer’s disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly understood. Here we report the purification of Aβ amyloid fibrils from meningeal Alzheimer’s brain tissue and their structural analysis with cryo-electron microscopy. We show that these fibrils are polymorphic but consist of similarly structured protofilaments. Brain derived Aβ amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed Aβ fibrils that were formed in vitro. These data underscore the importance to use patient-derived amyloid fibrils when investigating the structural basis of the disease.

Structural origin of polymorphism of Alzheimer's amyloid β-fibrils

2012 ◽  
Vol 447 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Audrey Agopian ◽  
Zhefeng Guo
Keyword(s):  
Amyloid Fibrils ◽  
Spin Exchange ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Side Chain ◽  
Resonance Spectroscopy ◽  
Amyloid Β Peptide ◽  
Amyloid Proteins ◽  
Aβ Amyloid

Formation of senile plaques containing amyloid fibrils of Aβ (amyloid β-peptide) is a pathological hallmark of Alzheimer's disease. Unlike globular proteins, which fold into unique structures, the fibrils of Aβ and other amyloid proteins often contain multiple polymorphs. Polymorphism of amyloid fibrils leads to different toxicity in amyloid diseases and may be the basis for prion strains, but the structural origin for fibril polymorphism is still elusive. In the present study we investigate the structural origin of two major fibril polymorphs of Aβ40: an untwisted polymorph formed under agitated conditions and a twisted polymorph formed under quiescent conditions. Using electron paramagnetic resonance spectroscopy, we studied the inter-strand side-chain interactions at 14 spin-labelled positions in the Aβ40 sequence. The results of the present study show that the agitated fibrils have stronger inter-strand spin–spin interactions at most of the residue positions investigated. The two hydrophobic regions at residues 17–20 and 31–36 have the strongest interactions in agitated fibrils. Distance estimates on the basis of the spin exchange frequencies suggest that inter-strand distances at residues 17, 20, 32, 34 and 36 in agitated fibrils are approximately 0.2 Å (1 Å=0.1 nm) closer than in quiescent fibrils. We propose that the strength of inter-strand side-chain interactions determines the degree of β-sheet twist, which then leads to the different association patterns between different cross β-units and thus distinct fibril morphologies. Therefore the inter-strand side-chain interaction may be a structural origin for fibril polymorphism in Aβ and other amyloid proteins.

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