TY - JOUR
T1 - Neuromelanin granules of the substantia nigra
T2 - proteomic profile provides links to tyrosine hydroxylase, stress granules and lysosomes
AU - Wulf, Maximilian
AU - Barkovits, Katalin
AU - Schork, Karin
AU - Eisenacher, Martin
AU - Riederer, Peter
AU - Gerlach, Manfred
AU - Eggers, Britta
AU - Marcus, Katrin
N1 - 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.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Laser microdissection
KW - Mass spectrometry
KW - Neuromelanin granules
KW - Neuromelanin synthesis
KW - Stress granules
KW - Substantia nigra pars compacta
KW - Tyrosine 3-Monooxygenase/metabolism
KW - Humans
KW - Lysosomes/metabolism
KW - Melanins/metabolism
KW - Substantia Nigra/metabolism
KW - Stress Granules
KW - Proteomics/methods
U2 - 10.1007/s00702-022-02530-4
DO - 10.1007/s00702-022-02530-4
M3 - Journal article
C2 - 35852604
AN - SCOPUS:85134502254
SN - 0300-9564
VL - 129
SP - 1257
EP - 1270
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 10
ER -