Proteomics

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Neuromelanin granules of the substantia nigra: proteomic profile provides links to tyrosine hydroxylase, stress granules and lysosomes


ABSTRACT: Neuromelanin is a black-brownish pigment, present in so-called neuromelanin granules (NMGs) in the cell bodies of dopaminergic neurons in the substantia nigra (SN) pars compacta. These neurons are lost in neurodegenerative diseases like Parkinson’s disease and dementia with Lewy bodies. Although it is known that lipids, proteins, and environmental toxins accumulate in NMGs, the function of NMGs has not yet been finally clarified as well as their origin and the synthesis of neuromelanin. We therefore isolated NMGs and surrounding SN tissue from control patients by laser microdissection and analyzed the proteomic profile by tandem mass spectrometry. With our improved workflow, we were able to 1) strengthen the regularly reported link between NMGs and lysosomes, 2) detect tyrosine hydroxylase to be highly abundant in NMGs, which may be related to neuromelanin synthesis and 3) indicate a yet undescribed link between stress granules (SGs) and NMGs. Based on our findings, we cautiously hypothesize, that SGs may be the origin of NMGs or form in close proximity to them, potentially due to the oxidative stress caused by neuromelanin-bound metals.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Midbrain Dopaminergic Neuron

SUBMITTER: Maximilian Wulf  

LAB HEAD: Katrin Marcus

PROVIDER: PXD033533 | Pride | 2022-08-29

REPOSITORIES: Pride

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Neuromelanin granules of the substantia nigra: proteomic profile provides links to tyrosine hydroxylase, stress granules and lysosomes.

Wulf Maximilian M   Barkovits Katalin K   Schork Karin K   Eisenacher Martin M   Riederer Peter P   Gerlach Manfred M   Eggers Britta B   Marcus Katrin K  

Journal of neural transmission (Vienna, Austria : 1996) 20220719 10


Neuromelanin is a black-brownish pigment, present in so-called neuromelanin granules (NMGs) in the cell bodies of dopaminergic neurons in the substantia nigra (SN) pars compacta. These neurons are lost in neurodegenerative diseases, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that lipids, proteins, and environmental toxins accumulate in NMGs, the function of NMGs has not yet been finally clarified as well as their origin and the synthesis of neuromelanin. We,  ...[more]

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