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Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson's disease and other synucleinopathies

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Exploring the pathological interaction between LRRK2 and alpha-synuclein

Alessandra Musso

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

Divergent alpha-synuclein solubility and aggregation properties in G2019S LRRK2 Parkinson's disease brains with Lewy Body pathology compared to idiopathic cases

Darren Moore

Mutations in LRRK2 are the most common genetic cause of Parkinson's disease (PD). The most prevalent LRRK2 mutation is the G2019S coding change, located in the kinase domain of this complex multi-domain protein. The majority of G2019S autopsy cases feature ...

Elsevier2013

Alpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies

Hilal Lashuel, Marc Moniatte, Bruno Claude Daniel Fauvet, Adrian Schmid

The development of novel therapies against neurodegenerative disorders requires the ability to detect their early, presymptomatic manifestations in order to enable treatment before irreversible cellular damage occurs. Precocious signs indicative of neurode ...

Amer Soc Biochemistry Molecular Biology Inc2013

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

Explaining the length threshold of polyglutamine aggregation

Paolo De Los Rios, Marc Hafner

The existence of a length threshold, of about 35 residues, above which polyglutamine repeats can give rise to aggregation and to pathologies, is one of the hallmarks of polyglutamine neurodegenerative diseases such as Huntington's disease. The reason why s ...

2012

Alpha-Synuclein Effects at the ER-to-Golgi Level and Potential Biomarkers in Rat Models of the Early Phase of Parkinson's Disease

Philippe Guillaume Coune

While Parkinson's disease has been described nearly 200 years ago, the mechanisms leading to the degeneration of selectively vulnerable populations of neurons, such as dopaminergic neurons in the substantia nigra, remain mostly unknown. Our poor understand ...

EPFL2011

Genetic Mouse Models of Neurodegenerative Diseases

Darren Moore, Alzbeta Trancikova, David Ramonet Jimenez

Neurodegenerative diseases are generally characterized by the selective degeneration of particular neuronal populations and the accumulation of abnormal or aggregated proteins within, but occasionally external to, neurons in affected brain regions. These d ...

2011

A better understanding of the molecular and cellular determinants that influence the pathology of Parkinson's disease (PD) is essential for developing effective diagnostic, preventative and therapeutic strategies to treat this devastating disease. A number ...

Elsevier2010

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Phosphorylation of alpha-synuclein (alpha-syn) at Ser-129 is a hallmark of Parkinson disease and related synucleinopathies. However, the identity of the natural kinases and phosphatases responsible for regulating alpha-syn phosphorylation remain unknown. H ...

American Society for Biochemistry and Molecular Biology2010

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Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease (AD). There is considerable consensus that the increased production and/or aggregation of alpha-synuclein (alpha-syn) plays a central role in the pathogenes ...

American Society for Biochemistry and Molecular Biology2010