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Exploring the pathological interaction between LRRK2 and alpha-synuclein

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Dopamine Transporter, PhosphoSerine129 alpha-Synuclein and alpha-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice

Salvatore Novello, Chiara Domenicale

The G2019S mutation in leucine rich-repeat kinase 2 (LRRK2) is a major cause of familial Parkinson's disease. We previously reported that G2019S knock-in mice manifest dopamine transporter dysfunction and phosphoSerine129 alpha-synuclein (pSer129 alpha-syn ...

MDPI2022

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Lewy bodies (LBs) are α-synuclein (α-syn)-rich intracellular inclusions that are an important pathological hallmark of Parkinson disease and several other neurodegenerative diseases. Increasing evidence suggests that the aggregation of α-syn has a central ...

2021

With the advent of the genetic era in Parkinson's disease (PD) research in 1997, alpha-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an econom ...

NATURE RESEARCH2021

Lewy bodies (LBs), one of the neuropathological defining hallmarks of Parkinson's disease (PD), are composed of a complex mixture of alpha-synuclein (aSyn) filaments and hundreds of proteins, lipids, and membranous organelles. However, these proteins' role ...

2021

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Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studi ...

2020

Glutaredoxin 1 Downregulation in the Substantia Nigra Leads to Dopaminergic Degeneration in Mice

Bernard Schneider

Background Parkinson's disease (PD) is characterized by a severe loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Perturbation of protein thiol redox homeostasis has been shown to play a role in the dysregulation of cell ...

2020

Nano-imaging trace elements at organelle levels in substantia nigra overexpressing alpha-synuclein to model Parkinson's disease

Bernard Schneider, Graham Knott, Philippe Colin

Sub-cellular trace element quantifications of nano-heterogeneities in brain tissues offer unprecedented ways to explore at elemental level the interplay between cellular compartments in neurodegenerative pathologies. We designed a quasi-correlative method ...

NATURE PUBLISHING GROUP2020

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

Hilal Lashuel, Graham Knott, Marion Leleu, Fabien Kuttler, Anne-Laure Mahul Mellier, Johannes Burtscher, Niran Maharjan, Laura Emmeline H Weerens

Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, t ...

2020

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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a kinase and GTPase, and PD-linked mutations are known to influence both enzymatic acti ...

NATL ACAD SCIENCES2020

A method for fast automated assessment of the magnetic resonance parkinsonism index

Bénédicte Marie Maréchal

In patients with parkinsonian syndromes, and particularly during the early stages of the clinical disease, differentiating between idiopathic Parkinson's disease and progressive supranuclear palsy is challenging. Imaging plays an important role in early di ...

SPRINGER2020