Engineering enhanced protein disaggregases for neurodegenerative disease

Targeting Hsp90/Hsp70-Based Protein Quality Control for Treatment of Adult Onset Neurodegenerative Diseases

(2015) William B. Pratt et al.   Annual Review of Pharmacology and Toxicology

The Hsp104 N-Terminal Domain Enables Disaggregase Plasticity and Potentiation

(2015) Elizabeth A. Sweeny et al.   MOLECULAR CELL

Potentiated Hsp104 Variants Antagonize Diverse Proteotoxic Misfolding Events

(2014) Meredith E. Jackrel et al.   CELL

Reversing deleterious protein aggregation with re-engineered protein disaggregases

(2014) Meredith E Jackrel et al.   CELL CYCLE

Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative disease-linked proteins

(2014) M. E. Jackrel et al.   Disease Models & Mechanisms

Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis

(2014) K L Jackson et al.   GENE THERAPY

Organismal proteostasis: role of cell-nonautonomous regulation and transcellular chaperone signaling

(2014) P. van Oosten-Hawle et al.   GENES & DEVELOPMENT

ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects

(2014) Haiyan Qiu et al.   JOURNAL OF CLINICAL INVESTIGATION

From yeast to patient neurons and back again: Powerful new discovery platforms

(2014) Daniel F. Tardiff et al.   MOVEMENT DISORDERS

Combating neurodegenerative disease with chemical probes and model systems

(2014) Priyanka Narayan et al.   Nature Chemical Biology

Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases

(2014) Jing L Guo et al.   NATURE MEDICINE

The amyloid state and its association with protein misfolding diseases

(2014) Tuomas P. J. Knowles et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The metazoan protein disaggregase and amyloid depolymerase system

(2014) Mariana P Torrente et al.   Prion

Calcineurin determines toxic versus beneficial responses to  -synuclein

(2014) G. Caraveo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae

(2014) S. M. Hill et al.   SCIENCE

Spatial quality control bypasses cell-based limitations on proteostasis to promote prion curing

(2014) Courtney L Klaips et al.   eLife

Super Spy variants implicate flexibility in chaperone action

(2014) Shu Quan et al.   eLife

Alpha-Synuclein Function and Dysfunction on Cellular Membranes

(2014) David Snead et al.   Experimental Neurobiology

Biology and Genetics of Prions Causing Neurodegeneration

(2013) Stanley B. Prusiner   Annual Review of Genetics

Tafamidis (Vyndaqel): A Light for FAP Patients

(2013) Susanna Nencetti et al.   ChemMedChem

Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress

(2013) Miguel Coelho et al.   CURRENT BIOLOGY

Rebels with a cause: molecular features and physiological consequences of yeast prions

(2013) David M. Garcia et al.   FEMS YEAST RESEARCH

Mutations in the 3′ untranslated region of FUS causing FUS overexpression are associated with amyotrophic lateral sclerosis

(2013) Mario Sabatelli et al.   HUMAN MOLECULAR GENETICS

Conserved Distal Loop Residues in the Hsp104 and ClpB Middle Domain Contact Nucleotide-binding Domain 2 and Enable Hsp70-dependent Protein Disaggregation

(2013) Morgan E. DeSantis et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Stress granules as crucibles of ALS pathogenesis

(2013) Yun R. Li et al.   JOURNAL OF CELL BIOLOGY

Harnessing the power of yeast to unravel the molecular basis of neurodegeneration

(2013) Sandra Tenreiro et al.   JOURNAL OF NEUROCHEMISTRY

Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy

(2013) Teresa Coelho et al.   JOURNAL OF NEUROLOGY

Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS

(2013) Hong Joo Kim et al.   NATURE

Self-propagation of pathogenic protein aggregates in neurodegenerative diseases

(2013) Mathias Jucker et al.   NATURE

Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress

(2013) Stéphanie Escusa-Toret et al.   NATURE CELL BIOLOGY

Therapeutic modulation of eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models

(2013) Hyung-Jun Kim et al.   NATURE GENETICS

Chaperone machines for protein folding, unfolding and disaggregation

(2013) Helen Saibil   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies

(2013) David J. Irwin et al.   NATURE REVIEWS NEUROSCIENCE

The changing scene of amyotrophic lateral sclerosis

(2013) Wim Robberecht et al.   NATURE REVIEWS NEUROSCIENCE

α-Synucleinopathy phenotypes

(2013) Heather McCann et al.   PARKINSONISM & RELATED DISORDERS

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor

(2013) J. Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Proliferation of amyloid- 42 aggregates occurs through a secondary nucleation mechanism

(2013) S. I. A. Cohen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Identification and Rescue of  -Synuclein Toxicity in Parkinson Patient-Derived Neurons

(2013) C. Y. Chung et al.   SCIENCE

Yeast Reveal a "Druggable" Rsp5/Nedd4 Network that Ameliorates  -Synuclein Toxicity in Neurons

(2013) D. F. Tardiff et al.   SCIENCE

Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders

(2013) Mark Hallett et al.   TOXICON

Evidence-based review and assessment of botulinum neurotoxin for the treatment of urologic conditions

(2013) Michael B. Chancellor et al.   TOXICON

Hsp104 Suppresses Polyglutamine-Induced Degeneration Post Onset in a Drosophila MJD/SCA3 Model

(2013) Mimi Cushman-Nick et al.   PLoS Genetics

Distinct TDP-43 pathology in ALS patients with ataxin 2 intermediate-length polyQ expansions

(2012) Michael P. Hart et al.   ACTA NEUROPATHOLOGICA

The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease

(2012) Oliver D. King et al.   BRAIN RESEARCH

Hsp104 Gives Clients the Individual Attention They Need

(2012) Amber N. Murray et al.   CELL

Operational Plasticity Enables Hsp104 to Disaggregate Diverse Amyloid and Nonamyloid Clients

(2012) Morgan E. DeSantis et al.   CELL

Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory

(2012) Amitabha Majumdar et al.   CELL

The Amyloid State of Proteins in Human Diseases

(2012) David Eisenberg et al.   CELL

Hsp104 Drives “Protein-Only” Positive Selection of Sup35 Prion Strains Encoding Strong [PSI+]

(2012) Morgan E. DeSantis et al.   CHEMISTRY & BIOLOGY

Metazoan Hsp70 machines use Hsp110 to power protein disaggregation

(2012) Heike Rampelt et al.   EMBO JOURNAL

Aneuploidy causes proteotoxic stress in yeast

(2012) A. B. Oromendia et al.   GENES & DEVELOPMENT

Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis

(2012) Julien Couthouis et al.   HUMAN MOLECULAR GENETICS

ALS-Associated Ataxin 2 PolyQ Expansions Enhance Stress-Induced Caspase 3 Activation and Increase TDP-43 Pathological Modifications

(2012) M. P. Hart et al.   JOURNAL OF NEUROSCIENCE

Prions are a common mechanism for phenotypic inheritance in wild yeasts

(2012) Randal Halfmann et al.   NATURE

Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation

(2012) Adrienne M Wang et al.   Nature Chemical Biology

Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models

(2012) Maria Armakola et al.   NATURE GENETICS

Tafamidis

(2012) Gerard Said et al.   NATURE REVIEWS DRUG DISCOVERY

A tightly regulated molecular toggle controls AAA+ disaggregase

(2012) Yuki Oguchi et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Tafamidis for transthyretin familial amyloid polyneuropathy: A randomized, controlled trial

(2012) T. Coelho et al.   NEUROLOGY

Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade

(2012) C. E. Bulawa et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Yeast Prion, Mod5, Promotes Acquired Drug Resistance and Cell Survival Under Environmental Stress

(2012) G. Suzuki et al.   SCIENCE

Evidence-based review and assessment of botulinum neurotoxin for the treatment of secretory disorders

(2012) Markus Naumann et al.   TOXICON

Botulinum neurotoxins: Mechanism of action

(2012) Ann P. Tighe et al.   TOXICON

Small Heat Shock Proteins Potentiate Amyloid Dissolution by Protein Disaggregases from Yeast and Humans

(2012) Martin L. Duennwald et al.   PLOS BIOLOGY

The elusive middle domain of Hsp104 and ClpB: Location and function

(2011) Morgan E. DeSantis et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments

(2011) Vivek Swarup et al.   BRAIN

FET proteins in frontotemporal dementia and amyotrophic lateral sclerosis

(2011) Ian R.A. Mackenzie et al.   BRAIN RESEARCH

Fine Tuning of a Biological Machine: DnaK Gains Improved Chaperone Activity by Altered Allosteric Communication and Substrate Binding

(2011) Regina S. Schweizer et al.   CHEMBIOCHEM

Understanding the role of TDP-43 and FUS/TLS in ALS and beyond

(2011) Sandrine Da Cruz et al.   CURRENT OPINION IN NEUROBIOLOGY

Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients

(2011) T. Lee et al.   HUMAN MOLECULAR GENETICS

Heat shock protein 104 inhibited the fibrillization of prion peptide 106–126 and disassembled prion peptide 106–126 fibrils in vitro

(2011) Ying-Hui Liu et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Different 8-Hydroxyquinolines Protect Models of TDP-43 Protein, α-Synuclein, and Polyglutamine Proteotoxicity through Distinct Mechanisms

(2011) Daniel F. Tardiff et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Model Organisms Reveal Insight into Human Neurodegenerative Disease: Ataxin-2 Intermediate-Length Polyglutamine Expansions Are a Risk Factor for ALS

(2011) Nancy M. Bonini et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Gain of function of mutant p53 by coaggregation with multiple tumor suppressors

(2011) Jie Xu et al.   Nature Chemical Biology

Dominant prion mutants induce curing through pathways that promote chaperone-mediated disaggregation

(2011) Susanne DiSalvo et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

The modulation of Amyotrophic Lateral Sclerosis risk by Ataxin-2 intermediate polyglutamine expansions is a specific effect

(2011) Suzana Gispert et al.   NEUROBIOLOGY OF DISEASE

Evaluating the prevalence of polyglutamine repeat expansions in amyotrophic lateral sclerosis

(2011) T. Lee et al.   NEUROLOGY

PolyQ Repeat Expansions in ATXN2 Associated with ALS Are CAA Interrupted Repeats

(2011) Zhenming Yu et al.   PLoS One

The Mammalian Disaggregase Machinery: Hsp110 Synergizes with Hsp70 and Hsp40 to Catalyze Protein Disaggregation and Reactivation in a Cell-Free System

(2011) James Shorter   PLoS One

RNA-binding proteins with prion-like domains in ALS and FTLD-U

(2011) Aaron D. Gitler et al.   Prion

Species-specific collaboration of heat shock proteins (Hsp) 70 and 100 in thermotolerance and protein disaggregation

(2011) M. Miot et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A yeast functional screen predicts new candidate ALS disease genes

(2011) J. Couthouis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protein-only mechanism induces self-perpetuating changes in the activity of neuronal Aplysia cytoplasmic polyadenylation element binding protein (CPEB)

(2011) S. U. Heinrich et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Single methyl group determines prion propagation and protein degradation activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p

(2011) D. Sharma et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chemical and Biological Approaches for Adapting Proteostasis to Ameliorate Protein Misfolding and Aggregation Diseases-Progress and Prognosis

(2011) S. L. Lindquist et al.   Cold Spring Harbor Perspectives in Biology

A Yeast Model of FUS/TLS-Dependent Cytotoxicity

(2011) Shulin Ju et al.   PLOS BIOLOGY

Molecular Determinants and Genetic Modifiers of Aggregation and Toxicity for the ALS Disease Protein FUS/TLS

(2011) Zhihui Sun et al.   PLOS BIOLOGY

α-Synuclein: Membrane Interactions and Toxicity in Parkinson's Disease

(2010) Pavan K. Auluck et al.   Annual Review of Cell and Developmental Biology

Applying Hsp104 to protein-misfolding disordersThis paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.

(2010) Shilpa Vashist et al.   Biochemistry and Cell Biology

Extensive FUS-Immunoreactive Pathology in Juvenile Amyotrophic Lateral Sclerosis with Basophilic Inclusions

(2010) Eric J. Huang et al.   BRAIN PATHOLOGY

Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation

(2010) Kausik Si et al.   CELL

ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import

(2010) Dorothee Dormann et al.   EMBO JOURNAL

Prion-like disorders: blurring the divide between transmissibility and infectivity

(2010) M. Cushman et al.   JOURNAL OF CELL SCIENCE

Directed Evolution of the DnaK Chaperone: Mutations in the Lid Domain Result in Enhanced Chaperone Activity

(2010) Raphael A. Aponte et al.   JOURNAL OF MOLECULAR BIOLOGY

The M-Domain Controls Hsp104 Protein Remodeling Activity in an Hsp70/Hsp40-Dependent Manner

(2010) Bernhard Sielaff et al.   JOURNAL OF MOLECULAR BIOLOGY

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia

(2010) Ian RA Mackenzie et al.   LANCET NEUROLOGY

Emergence and natural selection of drug-resistant prions

(2010) James Shorter   Molecular BioSystems

Two Parkinson's disease patients with α-synuclein gene duplication and rapid cognitive decline

(2010) Chae Won Shin et al.   MOVEMENT DISORDERS

Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

(2010) Andrew C. Elden et al.   NATURE

The prion hypothesis: from biological anomaly to basic regulatory mechanism

(2010) Mick F. Tuite et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

TAR DNA-binding protein 43 in neurodegenerative disease

(2010) Alice S. Chen-Plotkin et al.   Nature Reviews Neurology

Prion proteostasis

(2010) Elizabeth A. Sweeny et al.   Prion

Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast

(2010) K. A. Geiler-Samerotte et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CryoEM structure of Hsp104 and its mechanistic implication for protein disaggregation

(2010) S. Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation

(2010) J. Tyedmers et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Epigenetics in the Extreme: Prions and the Inheritance of Environmentally Acquired Traits

(2010) Randal Halfmann et al.   SCIENCE

Prions, protein homeostasis, and phenotypic diversity

(2010) Randal Halfmann et al.   TRENDS IN CELL BIOLOGY

Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans

(2010) Della C. David et al.   PLOS BIOLOGY

TARDBP 3′-UTR variant in autopsy-confirmed frontotemporal lobar degeneration with TDP-43 proteinopathy

(2009) Michael A. Gitcho et al.   ACTA NEUROPATHOLOGICA

A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic Proteins

(2009) Simon Alberti et al.   CELL

Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson's disease models

(2009) L. J. Su et al.   Disease Models & Mechanisms

Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis

(2009) G. S. Pesiridis et al.   HUMAN MOLECULAR GENETICS

N-terminal Domains Elicit Formation of Functional Pmel17 Amyloid Fibrils

(2009) Brenda Watt et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TDP-43 Is Intrinsically Aggregation-prone, and Amyotrophic Lateral Sclerosis-linked Mutations Accelerate Aggregation and Increase Toxicity

(2009) Brian S. Johnson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Motor Mechanism for Protein Threading through Hsp104

(2009) Petra Wendler et al.   MOLECULAR CELL

Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation

(2009) Lynette Cegelski et al.   Nature Chemical Biology

α-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity

(2009) Aaron D Gitler et al.   NATURE GENETICS

Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity

(2009) Esti Yeger-Lotem et al.   NATURE GENETICS

Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6

(2009) C. Vance et al.   SCIENCE

The TET Family of Proteins: Functions and Roles in Disease

(2009) A. Y. Tan et al.   Journal of Molecular Cell Biology

TDP-43A315T mutation in familial motor neuron disease

(2008) Michael A. Gitcho et al.   ANNALS OF NEUROLOGY

Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions

(2008) James Shorter et al.   EMBO JOURNAL

Peptide and Protein Binding in the Axial Channel of Hsp104

(2008) Ronnie Lum et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching

(2008) John J. Skinner et al.   JOURNAL OF CELL BIOLOGY

Hsp104 antagonizes α-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease

(2008) Christophe Lo Bianco et al.   JOURNAL OF CLINICAL INVESTIGATION

Diverse Pore Loops of the AAA+ ClpX Machine Mediate Unassisted and Adaptor-Dependent Recognition of ssrA-Tagged Substrates

(2008) Andreas Martin et al.   MOLECULAR CELL

Substrate threading through the central pore of the Hsp104 chaperone as a common mechanism for protein disaggregation and prion propagation

(2008) Peter Tessarz et al.   MOLECULAR MICROBIOLOGY

Protein disaggregation by the AAA+ chaperone ClpB involves partial threading of looped polypeptide segments

(2008) Tobias Haslberger et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity

(2008) B. S. Johnson et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis

(2008) J. Sreedharan et al.   SCIENCE