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Motor Deficits upon Alpha-Synuclein Expression in the Nigrostriatal System Are Due to a Loss of Dopaminergic Vesicles and Reduced Dopamine Release at an early Stage of Neurodegeneration

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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

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Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the ...

Oxford University Press2014

FOXO3 determines the accumulation of alpha-synuclein and controls the fate of dopaminergic neurons in the substantia nigra

Bernard Schneider, Graham Knott, Juan-Carlos Sarria, Lu Zheng, Emilda Pino, Ryoji Amamoto

Parkinson's disease (PD) is characterized by the selective degeneration of neuronal populations presumably due to pathogenic interactions between aging and predisposing factors such as increased levels of a-synuclein. Here, we genetically modulate the acti ...

Oxford University Press2014

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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). The clinical and neurochemical features of LRRK2-linked PD are similar to idiopathic disease although neuropathology is somewhat heter ...

Elsevier2014

Recombinant adeno-associated viral (AAV) vectors of serotypes 6, 8, and 9 were characterized as tools for gene delivery to dopaminergic neurons in the substantia nigra for future gene therapeutic applications in Parkinson's disease. While vectors of all th ...

Mary Ann Liebert2013

Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previous ...

Elsevier2013

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

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

Increased expression of α-synuclein and point mutations in its amino acid sequence play a causative role in familial forms of Parkinson's disease (PD). In addition, circumstances affecting the level of α-synuclein expression significantly increase the risk ...

EPFL2012

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Several lines of evidence suggest that phosphorylation of α-synuclein (α-syn) at S87 or S129 may play an important role in regulating its aggregation, fibrillogenesis, Lewy body formation, and neurotoxicity in vivo. However, whether phosphorylation at thes ...

2012