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The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Related publications (39)

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Recapitulating De Novo Alpha-Synuclein Fibrillization in a Novel Neuronal Model of Parkinson's Disease

Mohamed Bilal Fares

Athough it has been established for over 100 years that Lewy bodies (LBs) represent the major pathological hallmark of Parkinson's disease (PD), we still do not know why these fibrillar intra-neuronal inclusions of the α-Synuclein (α-Syn) protein form, and ...

EPFL2015

alpha-Synuclein strains cause distinct synucleinopathies after local and systemic administration

Michele Giugliano

Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions(1). The molecular hallmark of synucleinopathies such as Parkinson's disease, dement ...

Nature Publishing Group2015

Lack of additive role of ageing in nigrostriatal neurodegeneration triggered by alpha-synuclein overexpression

Grégoire Courtine, Laetitia Danielle Philippine Baud, Isabel Laura Vollenweider

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons as well as the presence of proteinaceous inclusions named Lewy bodies. alpha synuclein (alpha-syn) is a major constituent o ...

Biomed Central Ltd2015

Parkinson’s disease (PD) is the most common age-related neurodegenerative movement disorder that affects 1-2% of the general population over the age of 65 and rising to 4-5% over 80 years of age. It is estimated that 6.3 million people worldwide have Parki ...

EPFL2014

Parkin depletion delays motor decline dose-dependently without overtly affecting neuropathology in alpha-synuclein transgenic mice

Hilal Lashuel

Background: Mutations of the gene encoding the major component of Lewy bodies (LB), alpha-synuclein (alpha-syn), cause autosomal dominant forms of Parkinson's disease (PD), whereas loss-of-function mutations of the gene encoding the multifunctional E3 ubiq ...

BioMed Central2013

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

Hilal Lashuel, Abid Oueslati

Disorders characterized by α-synuclein (α-syn) accumulation, Lewy body formation and parkinsonism (and in some cases dementia) are collectively known as Lewy body diseases. The molecular mechanism (or mechanisms) through which α-syn abnormally accumulates ...

Nature Publishing Group2013

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Ubiquitination regulates, via different modes of modifications, a variety of biological processes, and aberrations in the process have been implicated in the pathogenesis of several neurodegenerative diseases. However, our ability to dissect the pathophysi ...

National Academy of Sciences2013

Elucidating the role of post-translational modifications of alpha-synuclein using semisynthesis

Mirva Hejjaoui

Alpha-synuclein (α-syn) is a natively unfolded protein that is closely linked to Parkinson’s disease (PD) by genetic, neuropathologic and biochemical evidence. Aggregated and fibrillar forms of α-syn are the main components of intracellular protein inclusi ...

EPFL2012

Neurodegenerative phenotypes in an A53T-synuclein transgenic mouse model are independent of LRRK2

Darren Moore, Alessandra Musso

Mutations in the genes encoding LRRK2 and -synuclein cause autosomal dominant forms of familial Parkinsons disease (PD). Fibrillar forms of -synuclein are a major component of Lewy bodies, the intracytoplasmic proteinaceous inclusions that are a pathologic ...

Oxford University Press2012

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Accumulation of misfolded alpha-synuclein (alpha S) is mechanistically linked to neurodegeneration in Parkinson's disease (PD) and other alpha-synucleinopathies. However, how alpha S causes neurodegeneration is unresolved. Because cellular accumulation of ...

Society for Neuroscience2012