This study investigates the effects of Vps35 p.D620N mutation on microglial function, showing increased LRRK2 kinase activity, chronic inflammation, and altered immune responses in mice.

bioRxiv · Sep 3, 2026 · PreprintNeuroscience

Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes

Adamantios Mamais, Richard D. Batchelor, Chairmandurai Aravindraja, Thomas B. Ladd, Austin J. Shute, Nitya Subrahmanian, Nunziata Maio, Chris D. Vulpe, Matthew J. LaVoie

This study shows that LRRK2 mutations disrupt iron homeostasis in neurons and astrocytes, leading to oxidative stress and ferroptosis.

Molecular Neurodegeneration · Jul 24, 2026Peer-reviewedNeuroscience

Peripheral inflammation mediates midbrain Lrrk2 kinase activity via Rab32 expression

Jordan Follett, Isaac Bul Deng, Robert C. Sharp, Shannon C. Wall, Adamantios Mamais, Matthew James Farrer

This study identifies Rab32 as a mediator linking peripheral inflammation to Lrrk2 kinase activity in microglia, with Tfe3 regulating Rab32 expression and Lrrk2 activation.

bioRxiv · Sep 5, 2025 · PreprintCell Biology

The LRRK2 kinase substrates Rab8a and Rab10 contribute complementary but distinct disease-relevant phenotypes in human neurons

Adamantios Mamais, Anwesha Sanyal, Austin Fajfer, Catherine G. Zykoski, Michael Guldin, Alexis Riley-DiPaolo, Nitya Subrahmanian, Whitney S. Gibbs, Steve Lin, Matthew J. LaVoie

This study shows that Rab8a and Rab10 deficiencies cause distinct lysosomal and Golgi defects in human neurons, with opposing effects on lysosomal pH and proteostasis of α-synuclein and tau.

Stem Cell Reports · Feb 1, 2024Peer-reviewedNeuroscience

Differential LRRK2 signalling and gene expression in WT-LRRK2 and G2019S-LRRK2 mouse microglia treated with zymosan and MLi2.

Iqra Nazish, Adamantios Mamais, Anna Mallach, Conceição Bettencourt, Alice Kaganovich, Thomas T. Warner, John Hardy, Patrick Alfryn Lewis, Jennifer M. Pocock, Mark Cookson, Rina Bandopadhyay

The paper examines gene expression changes in microglia from LRRK2-WT and G2019S knock-in mice treated with zymosan and MLi-2, identifying differential expression patterns and potential PD-related pathways.

Cells · Dec 26, 2023Peer-reviewedNeuroscience

Leucine-Rich Repeat Kinase 2 limits dopamine D1 receptor signaling in the striatum and biases against heavy persistent alcohol drinking

DANIEL NOBRE; NUNES DA SILVA, Aya Matsui, Erin M. Murray, Adamantios Mamais, Michael E. Authement, Jung Hoon Shin, Marlisa Shaw, Dorit Ron A, Mark Cookson, Veronica A. Alvarez

This study shows that LRRK2 in D1R-expressing striatal neurons reduces alcohol drinking by modulating D1R signaling and resilience to heavy drinking.

Neuropsychopharmacology · Sep 8, 2023Peer-reviewedNeuroscience

Sequential screening nominates the Parkinson's disease associated kinase LRRK2 as a regulator of Clathrin-mediated endocytosis

George R. Heaton, Natalie Landeck, Adamantios Mamais, Mike A. Nalls, Jonathon Nixon‐Abell, Ravindran Kumaran, Alexandra G. Beilina, Laura Pellegrini, Yan Li, Kirsten Harvey, Mark Cookson

The paper identifies LRRK2 as a regulator of clathrin-mediated endocytosis and links clathrin-trafficking pathways to Parkinson's disease risk.

Neurobiology of Disease · May 17, 2020Peer-reviewedMolecular Biology