The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease.

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The accumulation of aggregated α-synuclein in susceptible neurons in the brain, together with robust activation of nearby myeloid cells, are pathological hallmarks of Parkinson's disease (PD). While microglia represent the dominant type of myeloid cell in the brain, recent genetic and whole-transcriptomic studies have implicated another type of myeloid cell, bone-marrow derived monocytes, in disease risk and progression. Monocytes in circulation harbor high concentrations of the PD-linked enzyme leucine-rich repeat kinase 2 (LRRK2) and respond to both intracellular and extracellular aggregated α-synuclein with a variety of strong pro-inflammatory responses. This review highlights recent findings from studies that functionally characterize monocytes in PD patients, monocytes that infiltrate into cerebrospinal fluid, and emerging analyses of whole myeloid cell populations in the PD-affected brain that include monocyte populations. Central controversies discussed include the relative contribution of monocytes acting in the periphery from those that might engraft in the brain to modify disease risk and progression. We conclude that further investigation into monocyte pathways and responses in PD, especially the discovery of additional markers, transcriptomic signatures, and functional classifications, that better distinguish monocyte lineages and responses in the brain from other types of myeloid cells may reveal points for therapeutic intervention, as well as a better understanding of ongoing inflammation associated with PD.





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Strader, Samuel, and Andrew B West (2023). The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease. Biochemical Society transactions, 51(2). pp. 747–758. 10.1042/bst20201091 Retrieved from

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Andrew Bradley West

Professor of Pharmacology and Cancer Biology

I am a tenured Professor with a primary appointment in Pharmacology and Cancer Biology, secondary appointments in Neurology and Neurobiology, and I serve as the director of the Duke Center for Neurodegeneration and Neurotherapeutics. Our main research efforts in the laboratory have focused on LRRK2 and alpha-synuclein in critical mechanisms and biomarkers in neurodegeneration and as possible therapeutic targets for disease modification strategies. I am a founding member of the NINDS Parkinson Disease Biomarker Program (PDBP) steering committee, a past member of the Executive Scientific Advisory Board at the Michael J. Fox Foundation (MJFF), current member of the NSD-B study section for the NINDS Office of Translational Research, and I am a board-reviewing editor for neurodegeneration research for eLife.

In training, i performed undergraduate research in the laboratory of Todd Golde focused on mechanisms of Ab toxicity, thesis work in the laboratories of John Hardy and Matthew Farrer (Mayo Clinic Parkinson’s Udall Center) focused on the genetics and genomics of parkin-linked PD, and post-doctoral work with Nigel Maidment (UCLA Udall Center) and Ted and Valina Dawson (Johns Hopkins Parkinson Udall Center) focused on LRRK2-linked Parkinson disease. I was previously an F31 and F32 individual NRSA recipient and was selected in the first wave of NIH’s K99 pipeline in 2006. Funding from both NINDS and MJFF has been continuous since the West laboratory opened in Birmingham in 2008 and continued with the move to Duke University in late 2018.

I have authored more than 100 publications characterizing biochemical mechanisms underlying neurodegeneration and neurodevelopmental disorders. The West laboratory serves as a hub for LRRK2 and a-synuclein research through freely sharing novel antibodies, recombinant proteins, DNA plasmids, viral constructs, animals, and protocols with dozens of laboratories and pharmaceutical

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