LRRK2 in Parkinson disease: challenges of clinical trials

E Tolosa, M Vila, C Klein, O Rascol - Nature Reviews Neurology, 2020 - nature.com
One of the most common monogenic forms of Parkinson disease (PD) is caused by
mutations in the LRRK2 gene that encodes leucine-rich repeat kinase 2 (LRRK2). LRRK2 …

α-Synuclein pathology in Parkinson's disease and related α-synucleinopathies

MX Henderson, JQ Trojanowski, VMY Lee - Neuroscience letters, 2019 - Elsevier
Over 20 years ago, the synaptic protein α-synuclein was identified as the primary component
of the Lewy bodies (LBs) that are a sine qua non of Parkinson's disease (PD). Since that …

Spread of α-synuclein pathology through the brain connectome is modulated by selective vulnerability and predicted by network analysis

MX Henderson, EJ Cornblath, A Darwich, B Zhang… - Nature …, 2019 - nature.com
Studies of patients afflicted by neurodegenerative diseases suggest that misfolded proteins
spread through the brain along anatomically connected networks, prompting progressive …

[HTML][HTML] Advances in elucidating the function of leucine-rich repeat protein kinase-2 in normal cells and Parkinson's disease

M Taylor, DR Alessi - Current Opinion in Cell Biology, 2020 - Elsevier
Autosomal dominant missense mutations that hyperactivate the leucine-rich repeat protein
kinase-2 (LRRK2) are a common cause of inherited Parkinson's disease and therapeutic …

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein

C McKinnon, ML De Snoo, E Gondard… - Acta Neuropathologica …, 2020 - Springer
Parkinson's disease is a progressive neurodegenerative disorder characterised by the
accumulation of misfolded α-synuclein in selected brain regions, including the substantia …

LRRK2: autophagy and lysosomal activity

M Madureira, N Connor-Robson… - Frontiers in …, 2020 - frontiersin.org
It has been 15 years since the Leucine-rich repeat kinase 2 (LRRK2) gene was identified as
the most common genetic cause for Parkinson's disease (PD). The two most common …

Small-molecule LRRK2 inhibitors for PD therapy: Current achievements and future perspectives

J Hu, D Zhang, K Tian, C Ren, H Li, C Lin… - European Journal of …, 2023 - Elsevier
Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein that orchestrates a diverse
array of cellular processes, including vesicle transport, autophagy, lysosome degradation …

Aggregate-prone brain regions in Parkinson's disease are rich in unique N-terminus α-synuclein conformers with high proteolysis susceptibility

JA Wiseman, HC Murray, RLMF Faull… - npj Parkinson's …, 2024 - nature.com
In Parkinson's disease (PD), and other α-synucleinopathies, α-synuclein (α-Syn) aggregates
form a myriad of conformational and truncational variants. Most antibodies used to detect …

Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity

HA Lashuel, AL Mahul-Mellier, S Novello… - npj Parkinson's …, 2022 - nature.com
Antibodies against phosphorylated alpha-synuclein (aSyn) at S129 have emerged as the
primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral …

Autophagy and LRRK2 in the aging brain

F Albanese, S Novello, M Morari - Frontiers in neuroscience, 2019 - frontiersin.org
Autophagy is a highly conserved process by which long-lived macromolecules, protein
aggregates and dysfunctional/damaged organelles are delivered to lysosomes for …