Neuromelanin granules of the substantia nigra: proteomic profile provides links to tyrosine hydroxylase, stress granules and lysosomes.
Maximilian WulfKatalin BarkovitsKarin SchorkMartin EisenacherPeter RiedererManfred GerlachBritta EggersKatrin MarcusPublished in: Journal of neural transmission (Vienna, Austria : 1996) (2022)
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.
Keyphrases
- tandem mass spectrometry
- oxidative stress
- end stage renal disease
- spinal cord
- ultra high performance liquid chromatography
- high performance liquid chromatography
- chronic kidney disease
- simultaneous determination
- prognostic factors
- gas chromatography
- human health
- dna damage
- stem cells
- stress induced
- high resolution
- solid phase extraction
- mass spectrometry
- risk assessment
- ms ms
- spinal cord injury
- high speed
- climate change
- heat stress
- bone marrow
- patient reported
- heat shock protein