F. Tonelli

Pathogenic LRRK2 mutations cause loss of primary cilia and Neurturin in striatal Parvalbumin interneurons

The paper shows that LRRK2 mutations cause loss of primary cilia and Neurturin in striatal Parvalbumin interneurons, impairing neuroprotective signaling.

Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain

This study shows LRRK2 and PINK1 function in parallel neuroprotective pathways affecting ciliogenesis in Parkinson's disease, suggesting shared therapeutic targets.

Lysosome damage triggers acute formation of ER to lysosomes membrane tethers mediated by the bridge-like lipid transport protein VPS13C

The paper shows that VPS13C senses lysosome damage, relocates to lysosomes, and tethers them to the ER, suggesting a protective lipid transport response.

Genome-wide screen reveals Rab12 GTPase as a critical activator of pathogenic LRRK2 kinase

The paper identifies Rab12 as a critical activator of pathogenic LRRK2 kinase through a CRISPR-based screen and structural analysis.

Structural basis of human LRRK2 membrane recruitment and activation

This study determines cryo-EM structures of LRRK2-Rab29 complexes, revealing the structural basis of LRRK2 membrane recruitment and activation, and identifies potential targets for Parkinson's disease treatment.

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain

The paper shows that LRRK2 mutations and PPM1H loss cause cilia loss in neurons and astrocytes, disrupting Hedgehog signaling in the nigral-striatal pathway.

Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms

This study identifies distinct Rab proteins phosphorylated by LRRK1 and LRRK2, showing they are regulated by different mechanisms and respond differently to inhibitors.

Accurate MS-based Rab10 phosphorylation stoichiometry determination as readout for LRRK2 activity in Parkinson’s disease

The paper develops an ultra-sensitive MS-based assay to measure Rab10-Thr73 phosphorylation stoichiometry as a biomarker for LRRK2 activity in Parkinson’s disease.

PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

This study identifies PPM1H as a phosphatase that counteracts LRRK2 signaling by dephosphorylating Rab proteins, suggesting it as a potential therapeutic target for Parkinson's disease.

Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta

This study quantifies bone quality changes in Chihuahua zebrafish, showing similarities to human dominant osteogenesis imperfecta at multiple scales.