Dr. Marie McNeelyDec 6, 2023

What could be more exciting right now than listening to Dario Alessi share stories about his work unraveling the mysteries of how the LRRK2 gene contributes to Parkinson's disease? Nothing. Absolutely nothing. (At least in my opinion.)

https://open.spotify.com/episode/2x474VHmqJ7dfakk2fspcd

#neuroscience #scicomm #brain #parkinsonsdisease #parkinsons #genetics #research #science #podcast #podcasts #LRRK2

4: Elucidating the Pathobiology of LRRK2 in Parkinson's Disease with Dario Alessi

Listen to this episode from The Parkinson’s Research Podcast: New Discoveries in Neuroscience on Spotify. Mutations in the LRRK2 gene were first linked to Parkinson's disease (PD) risk in 2004. Since then, researchers from around the world have advanced our understanding of the mechanisms through which LRRK2 may contribute to PD, leading to the development of three potential LRRK2-targeted therapies that are now being evaluated in clinical trials. Along with colleagues and collaborators, Dr. Dario Alessi has pioneered new research and approaches that have aided in the development of drugs to inhibit LRRK2 and potentially treat people with Parkinson's disease. In this episode Dario discusses his work developing the LRRK2 kinase assay, LRRK2 Ser935 dephosphorylation assay, and Rab phosphorylation assay, as well as future directions and opportunities in the field. This year, Dario received the 2023 Robert A. Pritzker Prize for Leadership in Parkinson’s Research for his substantial research contribution and his commitment to mentoring the next generation of Parkinson’s scientists. Dario is the Professor of Signal Transduction and Science Director of the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee.This podcast is geared toward researchers and clinicians. If you live with Parkinson’s or have a friend or family member with PD, listen to The Michael J. Fox Foundation Parkinson’s Podcast. Hear from scientists, doctors and people with Parkinson's on different aspects of life with the disease as well as research toward treatment breakthroughs at https://www.michaeljfox.org/podcasts.

Spotify
Ron Beavis ❌Oct 17, 2023
α⧸ω ST phosphorylation diagrams for human and mouse leucine rich repeat kinase 2 (#LRRK2:p). The AF model for the human sequence shown has the prominent, complex phospho-IDR illustrated as a stringy region at the top of the structure between an ankyrin-like solenoid (left) & a leucine-rich repeat solenoid (right). As usual, the shape & orientation of the phospho-IDR in this model is not to be taken too seriously. #proteomics
The EMBO JournalJun 28, 2023
Regulation of #LRRK2 mRNA stability by ATIC and its substrate #AICAR through ARE-mediated mRNA decay in #Parkinson's disease
Yulan Xiong and coworkers
https://www.embopress.org/doi/full/10.15252/embj.2022113410
OsteoarthriticAutisticApr 15, 2023
‘Game-changing’ technique could identify Parkinson’s before symptoms show | The Independent
#Parkinsons
#ParkinsonsDiagnosis
#AlphaSyn
#AlphaSynSAA
#GBA
#LRRK2
#LossOfSmell
https://www.independent.co.uk/news/health/parkison-s-diagnosis-protein-study-symptoms-b2318504.html
‘Game-changing’ technique could identify Parkinson’s before symptoms show

New findings ‘lay the foundation for a biological diagnosis’ of Parkinson’s, scientists say

The Independent
Show threadThierry GalliMar 11, 2023
We found that the #Parkinson's disease related kinase #LRRK2 interacts with vesicular #SNAREs #VAMP4 and #VAMP7. #VAMP4 and #VAMP7 are required for proper processing and release of #Parkinson's disease #biomarkers #VGF as we found using #secretomics. We found late endosomal #secretion of #VGF together with #exosome markers like #CD63. We also developed a #rushassay to study #VGF #trafficking.
Thierry GalliMar 11, 2023
#Secretion of #VGF relies on the interplay between #LRRK2 and post-Golgi v-SNAREs #VAMP4 #VAMP7.
https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00232-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124723002322%3Fshowall%3Dtrue
Secretion of VGF relies on the interplay between LRRK2 and post-Golgi v-SNAREs

Filippini et al. report the direct interaction of leucine-rich repeat kinase 2 (LRRK2) with the endosomal vesicular SNAREs VAMP4 and VAMP7. LRRK2, VAMP4, and VAMP7 regulate the secretion of the Parkinson’s disease biomarker VGF. They provide evidence for the role of LRRK2 in regulating unconventional secretion in the disease.

Cell Reports
Thomas SandmannDec 21, 2022
New preprint from my colleagues at Denali: https://www.biorxiv.org/content/10.1101/2022.12.19.521070v1 They describe how the LRRK2 kinase, a risk factor for Parkinson's Disease regulates secretion of BMP, an endolysosomal lipid involved in glycosphingolipid (GSL) catabolism, from kidney into urine and modulates BMP and GSL levels in the brain. #neurodegeneration #lrrk2 #parkinsons #lipids #omics