Dataset Information

The Parkinson’s disease kinase LRRK2 impairs release sites of vulnerable dopamine axons -striatal synaptosomes phosphoproteomic study

ABSTRACT: We and others previously reported that knock-in mice expressing the pathogenic hyperactive Lrrk2G2019S mutation, exhibit deficits in dopamine release within the striatum. To investigate the underlying molecular mechanisms, we conducted quantitative phosphoproteomic Liquid Chromatography-Mass Spectrometry (LC-MS) studies on striatal synaptosomes from Lrrk2G2019S mice. Mice were treated with vehicle control or the potent and specific LRRK2 kinase inhibitor MLi-2, as pharmacological inhibition of the hyperactive Lrrk2G2019S kinase increases the likelihood of identifying in vivo changes in phosphoregulation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Chuyu Chen

LAB HEAD: Loukia Parisiadou

PROVIDER: PXD065006 | Pride | 2026-05-19

REPOSITORIES: Pride

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			Action	DRS
	020623-Loukia-mouse-synaptosome-MLi2-1-phos.raw	Raw
	020623-Loukia-mouse-synaptosome-MLi2-2-phos.raw	Raw
	020623-Loukia-mouse-synaptosome-MLi2-3-phos.raw	Raw
	020623-Loukia-mouse-synaptosome-Vehicle-1-phos.raw	Raw
	020623-Loukia-mouse-synaptosome-Vehicle-2-phos.raw	Raw

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Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.

Chen Chuyu C He Qianzi Q Tombesi Giulia G Napier Eve E Jaconelli Matthew M Moreno-Ramos Oscar Andrés OA Serio Hannah H Naaldijk Yahaira Y Promes Vanessa V Schneeweis Amanda A Quinn Kaitlyn K Nasios Christopher C Greggio Elisa E Kozorovitskiy Yevgenia Y Arango Daniel D Khan Amir R AR Alessi Dario R DR Dombeck Daniel A DA Hilfiker Sabine S Awatramani Rajeshwar R Parisiadou Loukia L

bioRxiv : the preprint server for biology 20250903

The end-stage pathology of Parkinson's disease (PD) involves the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). However, synaptic deregulation of these neurons begins much earlier. Understanding the mechanisms behind synaptic deficits is crucial for early therapeutic intervention, yet these remain largely unknown. In the SNc, different dopamine neuron subtypes show varying susceptibility patterns to PD, complicating our understanding. This study uses intersection ...[more]

PMID: 40909700

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