4.7 Article

Mechanisms of enhanced aggregation and fibril formation of Parkinson's disease-related variants of α-synuclein

Related references

Note: Only part of the references are listed.
Article Biology

The C-terminal tail of α-synuclein protects against aggregate replication but is critical for oligomerization

Azad Farzadfard et al.

Summary: Farzadfard et al. conducted a comprehensive analysis on a range of C-terminal truncations of aSN, revealing the importance of high C-terminus charge for decreased fibrillation rates. Truncated aSN showed decreased ability to form oligomers, disrupt synthetic vesicles, and exhibit cell toxicity, while still promoting or inhibiting aggregation through intramolecular interactions. Truncation of the C-terminal domain not only increased fibrillation tendency but also suppressed toxic oligomer formation, with changes in electrostatic potential serving as a double-edged safety guard.

COMMUNICATIONS BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Novel conformation-selective monoclonal antibodies against apoA-I amyloid fibrils

Takashi Ohgita et al.

Summary: Novel monoclonal antibodies (mAbs) generated in this study exhibit strong reactivity to amyloid fibrils formed by the 1-83 fragment of apoA-I, suggesting potential applications in both diagnosis of apoA-I-related amyloidosis and structural analysis of amyloid fibrils. These mAbs preferentially react with mature fibrils over non-fibrillar aggregates and recognize common structural features in apoA-I amyloid fibrils, as well as amyloid fibrils formed by alpha-synuclein.

FEBS JOURNAL (2021)

Article Multidisciplinary Sciences

In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers

Enrico Zurlo et al.

Summary: Understanding the mechanism of amyloid protein assembly is crucial for studying neurodegenerative diseases. EPR method can directly measure the amount of intermediates during the aggregation process without the need for separation, providing insights into the kinetics of intermediate species formation and conversion. The study on alpha-synuclein aggregation using EPR revealed a large population of short-lived primary oligomers formed directly from monomeric species.

PLOS ONE (2021)

Article Biochemistry & Molecular Biology

The role of water in the primary nucleation of protein amyloid aggregation

Jose D. Camino et al.

Summary: Water plays a key role in modulating the transition free energy of amyloid nucleation, governing the initiation of the process, and dictating the type of preferred primary nucleation and the type of amyloid polymorph generated. The initiation of amyloid aggregation likely results from a synergistic effect between protein intermolecular interactions and the properties of the water hydration layer of the protein surface. Primary nucleation can occur very rapidly in the bulk of the solution under conditions of poor water activity, leading to the generation of structurally distinct amyloid polymorphs.

BIOPHYSICAL CHEMISTRY (2021)

Article Chemistry, Multidisciplinary

Mechanism of Secondary Nucleation at the Single Fibril Level from Direct Observations of Aβ42 Aggregation

Manuela R. Zimmermann et al.

Summary: Understanding the mechanisms of amyloid formation and replication is crucial for studying neurodegenerative disorders like Alzheimer's disease. Secondary nucleation, which involves attachment of soluble species to fibril surfaces leading to the formation of new fibrils in solution, plays a key role in aggregate self-replication. This detailed insight into the process is essential for designing potential inhibitors of amyloid formation.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

Article Multidisciplinary Sciences

Structural insights into α-synuclein monomer-fibril interactions

Pratibha Kumari et al.

Summary: This study investigated the interaction between monomeric alpha-Syn and its fibrillar form using NMR and electron paramagnetic resonance spectroscopy, revealing that intermolecular interactions reduce intramolecular contacts in monomeric alpha-Syn, leading to further unfolding of its intrinsically disordered states and critically contributing to the aggregation kinetics of alpha-Syn during secondary nucleation.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Biochemistry & Molecular Biology

Role of α-Synuclein Regions in Nucleation and Elongation of Amyloid Fiber Assembly

Jose Gallardo et al.

ACS CHEMICAL NEUROSCIENCE (2020)

Article Multidisciplinary Sciences

Regulation of α-synuclein by chaperones in mammalian cells

Bjorn M. Burmann et al.

NATURE (2020)

Review Neurosciences

New insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy

Ricardo Guerrero-Ferreira et al.

CURRENT OPINION IN NEUROBIOLOGY (2020)

Review Biochemistry & Molecular Biology

The emerging role of ?-synuclein truncation in aggregation and disease

Zachary A. Sorrentino et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

Article Biochemistry & Molecular Biology

A short motif in the N-terminal region of α-synuclein is critical for both aggregation and function

Ciaran P. A. Doherty et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Article Chemistry, Multidisciplinary

α-Synuclein aggregation nucleates through liquid-liquid phase separation

Soumik Ray et al.

NATURE CHEMISTRY (2020)

Article Multidisciplinary Sciences

Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

Amberley D. Stephens et al.

NATURE COMMUNICATIONS (2020)

Review Medicine, Research & Experimental

Transmission of α-synuclein seeds in neurodegenerative disease: recent developments

Richard J. Karpowicz et al.

LABORATORY INVESTIGATION (2019)

Article Biochemistry & Molecular Biology

Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice

Jessica M. Froula et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

C-terminal -synuclein truncations are linked to cysteine cathepsin activity in Parkinson's disease

Ryan P. McGlinchey et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Mechanisms of aggregation and fibril formation of the amyloidogenic N-terminal fragment of apolipoprotein A-I

Chiharu Mizuguchi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Structural Insights into α-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations

Xiaodan Ni et al.

JOURNAL OF MOLECULAR BIOLOGY (2019)

Review Biochemistry & Molecular Biology

The physiological role of α-synuclein and its relationship to Parkinson's Disease

David Sulzer et al.

JOURNAL OF NEUROCHEMISTRY (2019)

Review Neurosciences

Alpha-synuclein structure and Parkinson's disease - lessons and emerging principles

Richard M. Meade et al.

MOLECULAR NEURODEGENERATION (2019)

Article Neurosciences

Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes

Sarah H. Shahmoradian et al.

NATURE NEUROSCIENCE (2019)

Review Biochemistry & Molecular Biology

α-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities

Parvez Alam et al.

JOURNAL OF NEUROCHEMISTRY (2019)

Article Multidisciplinary Sciences

Parkinson's disease is a type of amyloidosis featuring accumulation of amyloid fibrils of α-synuclein

Katsuya Araki et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Review Clinical Neurology

α-Synuclein and astrocytes: tracing the pathways from homeostasis to neurodegeneration in Lewy body disease

Zachary A. Sorrentino et al.

ACTA NEUROPATHOLOGICA (2019)

Review Chemistry, Multidisciplinary

Secondary nucleation in amyloid formation

Mattias Tornquist et al.

CHEMICAL COMMUNICATIONS (2018)

Article Biochemistry & Molecular Biology

The effect of truncation on prion-like properties of -synuclein

Makoto Terada et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Chemistry, Multidisciplinary

Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-beta peptide

Samuel I. A. Cohen et al.

NATURE CHEMISTRY (2018)

Article Chemistry, Multidisciplinary

C-terminal truncation of alpha-synuclein promotes amyloid fibril amplification at physiological pH

Ingrid M. van der Wateren et al.

CHEMICAL SCIENCE (2018)

Article Biology

Cryo-EM structure of alpha-synuclein fibrils

Ricardo Guerrero-Ferreira et al.

ELIFE (2018)

Review Biochemistry & Molecular Biology

Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms

Sofia Giorgetti et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

Article Multidisciplinary Sciences

SAR by kinetics for drug discovery in protein misfolding diseases

Sean Chia et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Multidisciplinary Sciences

Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel

Binsen Li et al.

NATURE COMMUNICATIONS (2018)

Article Biochemistry & Molecular Biology

Physiological C-terminal truncation of α-synuclein potentiates the prion-like formation of pathological inclusions

Zachary A. Sorrentino et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Biology

α-Synuclein Aggregation Monitored by Thioflavin T Fluorescence Assay

Michael M. Woerdehoff et al.

BIO-PROTOCOL (2018)

Review Neurosciences

Therapeutic approaches to target alpha-synuclein pathology

Patrik Brundin et al.

EXPERIMENTAL NEUROLOGY (2017)

Article Biochemistry & Molecular Biology

α-synuclein aggregation and its modulation

Dhiman Ghosh et al.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2017)

Review Biochemistry & Molecular Biology

α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies

Yvette C. Wong et al.

NATURE MEDICINE (2017)

Article Biochemistry & Molecular Biology

Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease

Zhentao Zhang et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

Article Chemistry, Multidisciplinary

Scaling behaviour and rate-determining steps in filamentous self-assembly

Georg Meisl et al.

CHEMICAL SCIENCE (2017)

Article Biochemistry & Molecular Biology

Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease

Zhentao Zhang et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2017)

Review Biochemistry & Molecular Biology

ThT 101: a primer on the use of thioflavin T to investigate amyloid formation

Kirsten Gade Malmos et al.

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS (2017)

Article Biochemistry & Molecular Biology

Perturbation in Long-Range Contacts Modulates the Kinetics of Amyloid Formation in α-Synuclein Familial Mutants

Priyatosh Ranjan et al.

ACS CHEMICAL NEUROSCIENCE (2017)

Review Neurosciences

More than a Rumor Spreads in Parkinson's Disease

Natalia C. Prymaczok et al.

FRONTIERS IN HUMAN NEUROSCIENCE (2016)

Review Biochemistry & Molecular Biology

Therapeutic approaches in Parkinson's disease andrelated disorders

Elvira Valera et al.

JOURNAL OF NEUROCHEMISTRY (2016)

Article Physics, Multidisciplinary

Physical determinants of the self-replication of protein fibrils

Andela Saric et al.

NATURE PHYSICS (2016)

Article Biochemical Research Methods

Molecular mechanisms of protein aggregation from global fitting of kinetic models

Georg Meisl et al.

NATURE PROTOCOLS (2016)

Article Chemistry, Physical

Estimation of the lag time in a subsequent monomer addition model for fibril elongation

Suzanne K. Shoffner et al.

PHYSICAL CHEMISTRY CHEMICAL PHYSICS (2016)

Article Multidisciplinary Sciences

Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation

Patrick Flagmeier et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Review Neurosciences

Versatile Structures of α-Synuclein

Chuchu Wang et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2016)

Article Multidisciplinary Sciences

Structure of the toxic core of α-synuclein from invisible crystals

Jose A. Rodriguez et al.

NATURE (2015)

Article Multidisciplinary Sciences

Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation

Alexander K. Buell et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Review Pharmacology & Pharmacy

Chemical kinetics for drug discovery to combat protein aggregation diseases

Paolo Arosio et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2014)

Article Clinical Neurology

Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease

Silke Appel-Cresswell et al.

MOVEMENT DISORDERS (2013)

Review Neurosciences

The many faces of alpha-synuclein: from structure and toxicity to therapeutic target

Hilal A. Lashuel et al.

NATURE REVIEWS NEUROSCIENCE (2013)

Article Clinical Neurology

Novel A18T and pA29S substitutions in α-synuclein may be associated with sporadic Parkinson's disease

Dorota Hoffman-Zacharska et al.

PARKINSONISM & RELATED DISORDERS (2013)

Article Clinical Neurology

Update on novel familial forms of Parkinson's disease and multiple system atrophy

Shinsuke Fujioka et al.

PARKINSONISM & RELATED DISORDERS (2013)

Article Multidisciplinary Sciences

Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism

Samuel I. A. Cohen et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Biochemistry & Molecular Biology

Mutant Protein A30P α-Synuclein Adopts Wild-type Fibril Structure, Despite Slower Fibrillation Kinetics

Luisel R. Lemkau et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Medicine, Research & Experimental

α-Synuclein in Parkinson's Disease

Leonidas Stefanis

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2012)

Article Multidisciplinary Sciences

In vivo demonstration that α-synuclein oligomers are toxic

Beate Winner et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

Review Biochemistry & Molecular Biology

Protein aggregation kinetics, mechanism, and curve-fitting: A review of the literature

Aimee M. Morris et al.

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2009)

Article Biochemistry & Molecular Biology

Observation of multiple intermediates in α-synuclein fibril formation by singular value decomposition analysis

Tomoaki Kamiyoshihara et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2007)

Article Neurosciences

Aggregated α-synuclein mediates dopaminergic neurotoxicity in vivo

Magali Periquet et al.

JOURNAL OF NEUROSCIENCE (2007)

Article Biochemistry & Molecular Biology

Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation

CW Bertoncini et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2005)

Article Multidisciplinary Sciences

Aggregation promoting C-terminal truncation of α-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations

WX Li et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Article Clinical Neurology

The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia

JJ Zarranz et al.

ANNALS OF NEUROLOGY (2004)

Article Biochemistry & Molecular Biology

α-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils

HA Lashuel et al.

JOURNAL OF MOLECULAR BIOLOGY (2002)

Article Multidisciplinary Sciences

Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease:: Implications for pathogenesis and therapy

KA Conway et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)