Journal ArticleDOI
Amyloid oligomers: A joint experimental/computational perspective on Alzheimer's disease, Parkinson's disease, type II diabetes, and amyotrophic lateral sclerosis
Phuong H. Nguyen,Ayyalusamy Ramamoorthy,Bikash R. Sahoo,Jie Zheng,Peter Faller,John E. Straub,Laura Dominguez,Joan-Emma Shea,Nikolay V. Dokholyan,Alfonso De Simone,Alfonso De Simone,Buyong Ma,Buyong Ma,Ruth Nussinov,Saeed Najafi,Son Tung Ngo,Antoine Loquet,Mara Chiricotto,Pritam Ganguly,James McCarty,Mai Suan Li,Carol K. Hall,Yiming Wang,Yifat Miller,Simone Melchionna,Birgit Habenstein,Stepan Timr,Jiaxing Chen,Brianna Hnath,Birgit Strodel,Rakez Kayed,Sylvain Lesné,Guanghong Wei,Fabio Sterpone,Andrew J. Doig,Philippe Derreumaux,Philippe Derreumaux +36 more
TLDR
In this paper, the authors review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease, Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research.Abstract:
Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo, and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP, and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D), and amyotrophic lateral sclerosis (ALS) research, respectively, for many years.read more
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Journal ArticleDOI
Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
Hebah Fatafta,Mohammed Khaled,Michael C. Owen,Michael C. Owen,Abdallah Sayyed-Ahmad,Birgit Strodel,Birgit Strodel +6 more
TL;DR: In this article, the authors carried out microseconds of all-atom molecular dynamics simulations on the dimerization of amyloid-β (Aβ)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes.
Journal ArticleDOI
Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications.
Yongchao Liu,Lili Teng,Baoli Yin,Hong-Min Meng,Xia Yin,Shuangyan Huan,Guosheng Song,Xiao-Bing Zhang +7 more
TL;DR: In this article , a review of the recent developments of activatable photoacoustic (PA) probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events is presented.
Journal ArticleDOI
Energy Landscapes of Protein Aggregation and Conformation Switching in Intrinsically Disordered Proteins.
TL;DR: In this paper, the authors discuss the characteristics of these multifunneled energy landscapes in detail, illustrated by molecular dynamics simulations that elucidated the underlying conformational transitions and aggregation processes.
Journal ArticleDOI
Amyloid β, Tau, and α-Synuclein aggregates in the pathogenesis, prognosis, and therapeutics for neurodegenerative diseases
Urmi Sengupta,Rakez Kayed +1 more
TL;DR: In this paper , the authors summarized the emerging evidence of Aβ, tau, and α-Syn aggregation in pathophysiology, and their overlap in a spectrum of neurodegenerative diseases including AD, PSP, PiD, CBD, PD and DLB.
Journal ArticleDOI
Binding to Amyloid-β Protein by Photothermal Blood-Brain Barrier-Penetrating Nanoparticles for Inhibition and Disaggregation of Fibrillation
Hao Geng,Yu-chen Pan,Ran Zhang,Dong Gao,Zijuan Wang,Boying Li,Ning Li,Dong-Sheng Guo,Chengfen Xing +8 more
TL;DR: NPs are multifunctional platforms for the inhibition of A β42 fibrillation and disaggregation of fibrils after irradiation with NIR light, distinctly reducing cytotoxicity and eliminating Aβ42 plaques in the hippocampus of AD mice.
References
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The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.