New in ACS Omega!
Integrating human substantia nigra single-nucleus data with phosphatome rewiring, structural modelling and LRRK2 phosphoproteomics identifies PFKFB2 as an LRRK2-linked metabolic node in Parkinson’s disease.
#Parkinsons #LRRK2 #PFKFB2
pubs.acs.org/acsodf/artic...
Integrating human substantia nigra single-nucleus data with phosphatome rewiring, structural modelling and LRRK2 phosphoproteomics identifies PFKFB2 as an LRRK2-linked metabolic node in Parkinson’s disease.
#Parkinsons #LRRK2 #PFKFB2
pubs.acs.org/acsodf/artic...
Single-Nucleus
Phosphatome Rewiring and Phosphoproteomics
Reveal PFKFB2 as an LRRK2-Linked Metabolic Node in Human Parkinsonian
Substantia Nigra
Abstract. Aberrant signaling
by leucine-rich repeat kinase 2 (LRRK2)
drives
Parkinson’s disease (PD) biology, linking Rab phosphorylation
to endolysosomal
pubs.acs.org
October 7, 2026 at 5:54 AM
New in ACS Omega!
Integrating human substantia nigra single-nucleus data with phosphatome rewiring, structural modelling and LRRK2 phosphoproteomics identifies PFKFB2 as an LRRK2-linked metabolic node in Parkinson’s disease.
#Parkinsons #LRRK2 #PFKFB2
pubs.acs.org/acsodf/artic...
Integrating human substantia nigra single-nucleus data with phosphatome rewiring, structural modelling and LRRK2 phosphoproteomics identifies PFKFB2 as an LRRK2-linked metabolic node in Parkinson’s disease.
#Parkinsons #LRRK2 #PFKFB2
pubs.acs.org/acsodf/artic...
Using cryo-ET, CRN Team Reck-Peterson showed that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules.
🔗 Read the full #preprint to learn more about their recent research: bit.ly/3VrVNaB
🔗 Read the full #preprint to learn more about their recent research: bit.ly/3VrVNaB
September 26, 2025 at 3:29 PM
Using cryo-ET, CRN Team Reck-Peterson showed that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules.
🔗 Read the full #preprint to learn more about their recent research: bit.ly/3VrVNaB
🔗 Read the full #preprint to learn more about their recent research: bit.ly/3VrVNaB
Congratulations to Amanda Bentley-DeSousa on the publication of her paper that defines how multiple lysosome stresses are integrated by the process known as CASM to activate LRRK2 signaling from lysosomes!!!
rupress.org/jcb/article/...
rupress.org/jcb/article/...
A STING–CASM–GABARAP pathway activates LRRK2 at lysosomes | Journal of Cell Biology | Rockefeller University Press
LRRK2 is a kinase whose activity is linked to Parkinson’s disease. This study identifies a pathway that links LRRK2 activation to lysosome perturbations. T
rupress.org
January 15, 2025 at 6:08 PM
Congratulations to Amanda Bentley-DeSousa on the publication of her paper that defines how multiple lysosome stresses are integrated by the process known as CASM to activate LRRK2 signaling from lysosomes!!!
rupress.org/jcb/article/...
rupress.org/jcb/article/...
LRRK2 is a kinase whose activity is linked to #Parkinsons disease. New research from Bentley-DeSousa and @shawnferguson.bsky.social reveals converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 and GABARAP. https://buff.ly/3DT8A02
January 15, 2025 at 7:46 PM
LRRK2 is a kinase whose activity is linked to #Parkinsons disease. New research from Bentley-DeSousa and @shawnferguson.bsky.social reveals converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 and GABARAP. https://buff.ly/3DT8A02
Extremely proud of Rebecca Wallings & Team in #TanseyLab3.0 for these high-impact findings in @sciencetranslationalmedicine www.science.org/doi/10.1126/...
The R1441C-Lrrk2 mutation induces myeloid immune cell exhaustion in an age- and sex-dependent manner in mice
The R1441C-Lrrk2 mutation causes age-acquired immune exhaustion in mouse macrophages in a sex-dependent manner.
www.science.org
November 24, 2024 at 8:56 PM
Extremely proud of Rebecca Wallings & Team in #TanseyLab3.0 for these high-impact findings in @sciencetranslationalmedicine www.science.org/doi/10.1126/...
Last week in #ScienceImmunology, Shengxiang Sun, Ta-Chiang Liu, & al. reported that certain variants in Crohn’s disease susceptibility genes lead to hyperactive LRRK2 in intestinal #macrophages that drive Paneth cell dysfunction. #Immunosky
Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction
Intestinal macrophage LRRK2 kinase activity impairs Paneth cell function in Crohn’s disease.
www.science.org
November 15, 2024 at 3:40 PM
Last week in #ScienceImmunology, Shengxiang Sun, Ta-Chiang Liu, & al. reported that certain variants in Crohn’s disease susceptibility genes lead to hyperactive LRRK2 in intestinal #macrophages that drive Paneth cell dysfunction. #Immunosky
Here’s our new review on: LRRK2, Lysosome Damage and Parkinson’s Disease
By knowing when, where and how LRRK2 kinase activity is turned on, we can better understand the relationship between excessive LRRK2 activity and Parkinson’s disease!
nam12.safelinks.protection.outlook.com?url=https%3A...
By knowing when, where and how LRRK2 kinase activity is turned on, we can better understand the relationship between excessive LRRK2 activity and Parkinson’s disease!
nam12.safelinks.protection.outlook.com?url=https%3A...
ScienceDirect.com | Science, health and medical journals, full text articles and books.
nam12.safelinks.protection.outlook.com
February 20, 2025 at 3:04 AM
Here’s our new review on: LRRK2, Lysosome Damage and Parkinson’s Disease
By knowing when, where and how LRRK2 kinase activity is turned on, we can better understand the relationship between excessive LRRK2 activity and Parkinson’s disease!
nam12.safelinks.protection.outlook.com?url=https%3A...
By knowing when, where and how LRRK2 kinase activity is turned on, we can better understand the relationship between excessive LRRK2 activity and Parkinson’s disease!
nam12.safelinks.protection.outlook.com?url=https%3A...
New research led by Devin Clegg that defines how lysosome swelling and lysosome deacidification evoke distinct routes for LRRK2 activation: doi.org/10.1101/2025...
LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses
Increased activity of leucine-rich repeat kinase 2 (LRRK2) is an important risk factor for Parkinson’s disease. LRRK2 localizes to lysosomal membranes, and changes in lysosome physiology are emerging ...
doi.org
December 9, 2025 at 2:06 AM
New research led by Devin Clegg that defines how lysosome swelling and lysosome deacidification evoke distinct routes for LRRK2 activation: doi.org/10.1101/2025...
Nice paper by Ji Sun and Dario Alessi labs describing multiple distinct Rab GTPase binding sites in the LRRK2 kinase involved in Parkinson Disease.
May 5, 2026 at 10:40 PM
Nice paper by Ji Sun and Dario Alessi labs describing multiple distinct Rab GTPase binding sites in the LRRK2 kinase involved in Parkinson Disease.
Tamara from our lab will present some unusual findings about Lrrk2 @ascbiology.bsky.social meeting #CellBio2024
December 12, 2024 at 5:19 AM
Tamara from our lab will present some unusual findings about Lrrk2 @ascbiology.bsky.social meeting #CellBio2024
Happy to share our new work on LRRK2 and PINK1 signalling in the brain. The two kinases appear to work on parallel pathway, but both converging on cilia. PINK1 KO animals have shorter and fewer cilia in striatal cholinergic interneurons and less GDNF.
www.pnas.org/doi/10.1073/...
www.pnas.org/doi/10.1073/...
Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain | PNAS
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1)
are associated with familial Parkinson’s disease (PD). LRRK2 ph...
www.pnas.org
January 29, 2025 at 12:15 PM
Happy to share our new work on LRRK2 and PINK1 signalling in the brain. The two kinases appear to work on parallel pathway, but both converging on cilia. PINK1 KO animals have shorter and fewer cilia in striatal cholinergic interneurons and less GDNF.
www.pnas.org/doi/10.1073/...
www.pnas.org/doi/10.1073/...
Bentley-DeSousa, Roczniak-Ferguson and @shawnferguson.bsky.social reveal converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 & GABARAP rupress.org/jcb/article/...
📕 From The Year In Cell Biology: rupress.org/jcb/collecti...
#CellBio2025
📕 From The Year In Cell Biology: rupress.org/jcb/collecti...
#CellBio2025
December 4, 2025 at 6:15 PM
Bentley-DeSousa, Roczniak-Ferguson and @shawnferguson.bsky.social reveal converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 & GABARAP rupress.org/jcb/article/...
📕 From The Year In Cell Biology: rupress.org/jcb/collecti...
#CellBio2025
📕 From The Year In Cell Biology: rupress.org/jcb/collecti...
#CellBio2025
Extracellular vesicle-mediated release of bis(monoacylglycerol)phosphate is regulated by LRRK2 and glucocerebrosidase activity
Extracellular vesicle-mediated release of bis(monoacylglycerol)phosphate is regulated by LRRK2 and glucocerebrosidase activity
Dysregulated exocytosis of bis(monoacylglycerol)phosphate (BMP)-enriched extracellular vesicles driven by pathogenic LRRK2 activity supports elevated urinary BMP levels and its use as a biomarker for...
buff.ly
April 19, 2026 at 8:21 AM
Extracellular vesicle-mediated release of bis(monoacylglycerol)phosphate is regulated by LRRK2 and glucocerebrosidase activity
More insights into the genetics of LRRK2 in Parkinson's from the @asapresearch.bsky.social GP2 project
doi.org/10.1038/s415...
doi.org/10.1038/s415...
The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson’s disease - npj Parkinson's Disease
npj Parkinson's Disease - The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson’s disease
doi.org
November 14, 2024 at 10:13 PM
More insights into the genetics of LRRK2 in Parkinson's from the @asapresearch.bsky.social GP2 project
doi.org/10.1038/s415...
doi.org/10.1038/s415...
Great new study from Liu lab @WUSTL dissecting the interaction between #autophagy, cigarette smoke, and #IBD risk mutations #LRRK2 #ATG16L1 driving Paneth cell defects through macrophages www.science.org/doi/10.1126/...
November 16, 2024 at 7:31 AM
Great new study from Liu lab @WUSTL dissecting the interaction between #autophagy, cigarette smoke, and #IBD risk mutations #LRRK2 #ATG16L1 driving Paneth cell defects through macrophages www.science.org/doi/10.1126/...
Understanding #Parkinsons subtypes is key to more targeted RCTs & better therapeutics! 🧠 Our new study finds that LRRK2 PD patients show milder cortical atrophy, with preserved temporal & occipital regions compared to sporadic PD. #LRRK2 #dataviz
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
March 12, 2025 at 1:57 PM
Understanding #Parkinsons subtypes is key to more targeted RCTs & better therapeutics! 🧠 Our new study finds that LRRK2 PD patients show milder cortical atrophy, with preserved temporal & occipital regions compared to sporadic PD. #LRRK2 #dataviz
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
📣 New #publications from CRN Team Alessi!
⬅️ They tested the LRRK2 inhibitor MLi-2 in a model of early stage, LRRK2 mutation–associated PD.
🔗 bit.ly/41nFBdA
➡️ They discovered that phosphatase PPM1M counteracts LRRK2 and identified a genetic variant in PPM1M present in PD.
🔗 bit.ly/4nkRVnR
⬅️ They tested the LRRK2 inhibitor MLi-2 in a model of early stage, LRRK2 mutation–associated PD.
🔗 bit.ly/41nFBdA
➡️ They discovered that phosphatase PPM1M counteracts LRRK2 and identified a genetic variant in PPM1M present in PD.
🔗 bit.ly/4nkRVnR
August 26, 2025 at 3:54 PM
📣 New #publications from CRN Team Alessi!
⬅️ They tested the LRRK2 inhibitor MLi-2 in a model of early stage, LRRK2 mutation–associated PD.
🔗 bit.ly/41nFBdA
➡️ They discovered that phosphatase PPM1M counteracts LRRK2 and identified a genetic variant in PPM1M present in PD.
🔗 bit.ly/4nkRVnR
⬅️ They tested the LRRK2 inhibitor MLi-2 in a model of early stage, LRRK2 mutation–associated PD.
🔗 bit.ly/41nFBdA
➡️ They discovered that phosphatase PPM1M counteracts LRRK2 and identified a genetic variant in PPM1M present in PD.
🔗 bit.ly/4nkRVnR
Phase 2b LUMA trial that tested BIIB122/DNL151, an oral brain-penetrant inhibitor of LRRK2, as a potential disease-modifying therapy in 648 participants with early-stage Parkinson’s disease. Results just announced in Seoul this week. Unfortunately negative.
www.mdscongress.org/Abstracts/La...
www.mdscongress.org/Abstracts/La...
October 6, 2026 at 1:19 PM
Phase 2b LUMA trial that tested BIIB122/DNL151, an oral brain-penetrant inhibitor of LRRK2, as a potential disease-modifying therapy in 648 participants with early-stage Parkinson’s disease. Results just announced in Seoul this week. Unfortunately negative.
www.mdscongress.org/Abstracts/La...
www.mdscongress.org/Abstracts/La...
Now online! The structural basis for LRRK2’s activation and autoinhibition
The structural basis for LRRK2’s activation and autoinhibition
Elevated kinase activity in leucine-rich repeat kinase 2 (LRRK2) is linked to Parkinson’s disease; this study shows that its ROC GTPase acts as a nucleotide-dependent molecular switch that regulates activation and autoinhibition and reveals how some but not all PD mutations disrupt this regulatory switch.
dlvr.it
August 10, 2026 at 2:59 PM
Now online! The structural basis for LRRK2’s activation and autoinhibition
New CRN Team Desjardins #preprint and #publication!
⬅️ LRRK2(G2019S) disrupts iron balance in macrophages, blocking ferritinophagy under iron overload bit.ly/47VzxvC
➡️ LRRK2(G2019S) mutant mice show stronger gut inflammation post-infection, linking gut immune changes to early PD bit.ly/3LVKlCk
⬅️ LRRK2(G2019S) disrupts iron balance in macrophages, blocking ferritinophagy under iron overload bit.ly/47VzxvC
➡️ LRRK2(G2019S) mutant mice show stronger gut inflammation post-infection, linking gut immune changes to early PD bit.ly/3LVKlCk
November 17, 2025 at 3:59 PM
New CRN Team Desjardins #preprint and #publication!
⬅️ LRRK2(G2019S) disrupts iron balance in macrophages, blocking ferritinophagy under iron overload bit.ly/47VzxvC
➡️ LRRK2(G2019S) mutant mice show stronger gut inflammation post-infection, linking gut immune changes to early PD bit.ly/3LVKlCk
⬅️ LRRK2(G2019S) disrupts iron balance in macrophages, blocking ferritinophagy under iron overload bit.ly/47VzxvC
➡️ LRRK2(G2019S) mutant mice show stronger gut inflammation post-infection, linking gut immune changes to early PD bit.ly/3LVKlCk
New in-cell cryo-electron tomography research reveals differential effects of type I & type II kinase inhibitors on #Parkinsons -associated LRRK2 filament formation & microtubule association
elifesciences.org/articles/111...
elifesciences.org/articles/111...
July 28, 2026 at 10:16 PM
New in-cell cryo-electron tomography research reveals differential effects of type I & type II kinase inhibitors on #Parkinsons -associated LRRK2 filament formation & microtubule association
elifesciences.org/articles/111...
elifesciences.org/articles/111...
Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation
Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation
Fricke et al. find that knockout of the RAB phosphatase PPM1H disrupts axonal autophagosome transport, impairs autophagosomal degradation of axonal α-synuclein, and exacerbates PFF-seeded α-synuclein aggregation in a LRRK2-dependent manner, linking dysregulation of the LRRK2-pRAB-PPM1H axis to defective axonal autophagy and α-synuclein pathology.
dlvr.it
May 30, 2026 at 11:23 PM
Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation
ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes www.biorxiv.org/content/10.1...
ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes
Increased activity of leucine-rich repeat kinase 2 (LRRK2) confers Parkinson's disease risk. LRRK2 dynamically localizes to lysosomal membranes in response to various stresses, yet the mechanisms by w...
www.biorxiv.org
August 30, 2026 at 3:17 PM
ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes www.biorxiv.org/content/10.1...
In this study, CRN Team De Camilli identifies STING as an activator of LRRK2 via the conjugation of ATG8 to a single membrane pathway.
🔗 Check out the full #publication: rupress.org/jcb/article/...
🔗 Check out the full #publication: rupress.org/jcb/article/...
February 27, 2025 at 4:38 PM
In this study, CRN Team De Camilli identifies STING as an activator of LRRK2 via the conjugation of ATG8 to a single membrane pathway.
🔗 Check out the full #publication: rupress.org/jcb/article/...
🔗 Check out the full #publication: rupress.org/jcb/article/...
Having recently defined a STING -CASM-GABARAP pathway for LRRK2 activation (doi.org/10.1083/jcb...., doi.org/10.1016/j.ce...), it was satisfying to see this new publication that independently lands on STING and GABARAP as LRRK2 activators: doi.org/10.1073/pnas...
STING-induced noncanonical autophagy regulates endolysosomal homeostasis | PNAS
The cGAS–STING pathway mediates innate immune responses to cytosolic DNA. In addition
to its well-established role in inducing inflammatory cytokin...
doi.org
February 25, 2025 at 9:37 PM
Having recently defined a STING -CASM-GABARAP pathway for LRRK2 activation (doi.org/10.1083/jcb...., doi.org/10.1016/j.ce...), it was satisfying to see this new publication that independently lands on STING and GABARAP as LRRK2 activators: doi.org/10.1073/pnas...