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

Maximilian Wulf, Katalin Barkovits, Karin Schork, Martin Eisenacher, Peter Riederer, Manfred Gerlach, Britta Eggers, Katrin Marcus*

*Kontaktforfatter

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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, 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, 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.

OriginalsprogEngelsk
TidsskriftJournal of Neural Transmission
Vol/bind129
Udgave nummer10
Sider (fra-til)1257-1270
ISSN0300-9564
DOI
StatusUdgivet - okt. 2022

Bibliografisk note

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. This work was supported by de.NBI, a project of the German Federal Ministry of Education and Research (BMBF) (grant number FKZ 031 A 534A) and P.U.R.E. (Protein Research Unit Ruhr within Europe) and Center for Protein Diagnostics (ProDi) grants, both from the Ministry of Innovation, Science and Research of North-Rhine Westphalia, Germany.

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