Andrew B. West

Rab12 is a regulator of mitophagy and mitochondrial homeostasis

This study identifies Rab12 as a negative regulator of mitophagy and mitochondrial homeostasis, showing its loss increases mitochondrial clearance and sensitivity to stress.

Lysosomal swelling triggers LRRK2 activity

This study identifies lysosomal swelling as a trigger for LRRK2-mediated Rab phosphorylation, independent of membrane damage or PIKfyve inhibition.

Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies

This study shows that LRRK2-mediated phosphorylation of Rab12 accumulates in lysosomal-like structures in tauopathies and synucleinopathies, linking LRRK2 kinase activity to endolysosomal dysfunction.

Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases

This study reports the atomic structure of mouse α-synuclein fibrils and shows they differ structurally and functionally from human fibrils linked to Parkinson's and MSA.

Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation

The paper measures LRRK2 kinase activity via pT73-Rab10 in serum, linking it to inflammation and Parkinson's disease severity.

Gut mucosal cells transfer alpha-synuclein to the vagus nerve

The paper shows that gut mucosal cells can transfer alpha-synuclein to the vagus nerve, suggesting a non-neuronal source of fibrillar alpha-synuclein in Parkinson's disease.

Structural and functional landscape of α-synuclein fibril conformations amplified from cerebrospinal fluid

The paper identifies six novel α-synuclein fibril assemblies from cerebrospinal fluid samples and shows they have distinct functional properties despite no single structural feature predicting their function.

Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein

This study shows that inhibiting LRRK2 kinase activity increases α-synuclein presynaptic localization and anterograde axonal transport in neurons.

Age-Associated Insolubility of Parkin in Human Midbrain is Linked to Redox Balance and Sequestration of Reactive Dopamine Metabolites

This study investigates how parkin's redox state and insolubility in human midbrain relate to oxidative stress and dopamine metabolism, showing that parkin's cysteine modifications affect H2O2 levels and neuroprotection.

Dopaminergic Neurodegeneration Induced by Parkinson's Disease-Linked G2019S LRRK2 is Dependent on Kinase and GTPase Activity

This study develops a rat model of Parkinson's disease caused by the G2019S LRRK2 mutation and shows that kinase and GTPase activities are critical for neurodegeneration.

Pathologic α-Synuclein Species Activate LRRK2 in Pro-Inflammatory Monocyte and Macrophage Responses

The paper shows that α-synuclein fibrils activate LRRK2 kinase in monocyte-derived macrophages, linking LRRK2 mutations to pro-inflammatory responses in Parkinson's disease.

Oxidative Modifications of Parkin Underlie its Selective Neuroprotection in Adult Human Brain

This study identifies oxidative modifications of parkin in adult human brain that confer neuroprotection by reducing H2O2, conjugating dopamine radicals, and forming neuromelanin.

Pharmacodynamic Markers of LRRK2 Inhibition in Biofluids

This study identifies biofluid markers of LRRK2 inhibition in non-human primates using three LRRK2 inhibitors, showing reduced pS935-LRRK2 and exosome LRRK2 in blood, urine, and CSF.