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Comparison of MSA with PD/DLB alpha-synuclein pathology using proximity proteomics

ABSTRACT: Multiple systems atrophy (MSA) is a unique synucleinopathy of unknown cause characterized by alpha-synuclein aggregates in oligodendroglia. Here, we used the in-situ proximity labeling technique biotinylation (BAR) by antibody recognition to identify alpha-synuclein interactomes in the MSA brain and compare them with other common synucleinopathies.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Parkinson's Disease

SUBMITTER: Bryan Killinger

LAB HEAD: Bryan Killinger

PROVIDER: PXD055305 | Pride | 2025-03-27

REPOSITORIES: Pride

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	20221223_bbm1840_23-3052_Killinger_01.raw	Raw
	20221223_bbm1840_23-3052_Killinger_02.raw	Raw
	20221223_bbm1840_23-3052_Killinger_03.raw	Raw
	20221223_bbm1840_23-3052_Killinger_04.raw	Raw
	20221223_bbm1840_23-3052_Killinger_05.raw	Raw

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Publications

Proximity proteomics reveals unique and shared pathological features between multiple system atrophy and Parkinson's disease.

Choi Solji G SG Tittle Tyler R TR Barot Raj R RR Betts Dakota J DJ Gallagher Johnie J JJ Kordower Jeffrey H JH Chu Yaping Y Killinger Bryan A BA

Acta neuropathologica communications 20250323 1

Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are neurodegenerative diseases with shared clinical and pathological features. Aggregates of alpha-synuclein (αsyn) phosphorylated at serine 129 (PSER129) are hallmarks of synucleinopathies, which, for PD/DLB, are found predominantly in neurons, whereas in MSA, aggregates are primarily found in oligodendroglia. It remains unclear whether the distinct pathological presentations o ...[more]

PMID: 40122840

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Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Î±-synucleinopathy, characterized by prominent Î±-synuclein accumulation in oligodendrocytes. In this study we investigated mRNA expression in substantia nigra of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nagra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.

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microRNA profiling by high-throughput sequencing in the substantia nigra and striatum of Multiple System Atrophy (MSA) transgenic mice and wild type controls

Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Ia-synucleinopathy, characterized by prominent Ia-synuclein accumulation in oligodendrocytes. In this study we investigated miRNA expression in the substantia nigra and striatum of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nigra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.

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2016-03-15 | E-MTAB-3986 | biostudies-arrayexpress

In Situ Proximity Labeling Identifies Lewy Pathology Molecular Interactions in the Human Brain

Project description:The intracellular misfolding and accumulation of alpha-synuclein into structures collectively called LP is a central phenomenon for the pathogenesis of synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Understanding the molecular architecture of LP is crucial for understanding synucleinopathy disease origins and progression. Here we used a technique called biotinylation by antibody recognition (BAR) to label total (BAR-SYN1) and pathological alpha-synuclein (BAR-PSER129) in situ for subsequent mass spectrometry analysis. This technique has broad potential to help understand the phenomenon of LP in primary human tissue and animal models.

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2023-07-17 | GSE235418 | GEO

Proteomic characterization of neuromelanin granules and substantia nigra in health and disease

Project description:Neuromelanin is a black-brownish pigment, present in so-called neuromelanin granules (NMG) in the cell bodies of dopaminergic neurons in the substantia nigra. These neurons are lost in neurodegenerative diseases like Parkinson’s disease and dementia with Lewy bodies (DLB). Although it is known that lipids, proteins, and environmental toxins accumulate in NMG, the function of NMG in health and disease remains elusive, as well as the synthesis of neuromelanin. We therefore isolated NMG and surrounding SN tissue from control and DLB patients by laser micro-dissection and analyzed the proteomic profile by tandem-mass spectrometry. The NMG core proteome consisted of several proteins specific for stress granules regardless of health status, indicating a potential, yet unknown, association of NMG and stress granules. Potential-disease related proteomic alterations lead us to the hypothesis of an eventual impairment of the lipid metabolism, as associated proteins were lower abundant in SN tissue of DLB patients. Furthermore, α-synuclein was found to be specifically higher abundant in NMG of DLB patients. As α-synuclein is known to form neurotoxic aggregates, the accumulation inside of NMG suggests a neuroprotective role of NMG in synucleinopathies. With our results, we are able to propose alternative hypotheses on NMG origin and function.

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