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A spatially resolved view on the aging substantia nigra: an exploratory proteomic study

ABSTRACT: Physiological ageing is accompanied by numerous structural and molecular changes in the brain, with varying degrees in different brain areas, and is therefore considered one of the major risk factors for neurodegenerative diseases. As early pathomechanisms of neurodegeneration are often difficult to assess, analysing the ageing brain and its substructures may lead to insights into earliest alterations eventually leading to neurodegeneration. The present study focuses on elucidating age-related changes in the substantia nigra pars compacta, a brain region particularly vulnerable in Parkinson’s disease and its substructures. With a particular emphasis on neuromelanin granules we aimed to gain a spatially resolved view on aging-dependent alterations to draw conclusions on early processes potentially leading to neurodegeneration. Our findings, which included the identification of reduced levels of proteins involved in dopaminergic neurotransmission, suggest either a specific loss of dopaminergic neurons or a reduction in metabolic activity. Furthermore, we observed alterations in the abundances of mitochondrial proteins that are potentially indicative of an age-related shift in their localization within aged tissue donors. Consequently, the present exploratory study suggests that proteomic changes, frequently referred to as potential pathomechanisms of PD, namely dopaminergic dysfunction and aberrations in the mitochondrial population, are already occurring in the physiological aging process of the human SN

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Britta Eggers

LAB HEAD: Katrin Marcus

PROVIDER: PXD061756 | Pride | 2025-09-23

REPOSITORIES: Pride

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	FLI12093.raw	Raw
	FLI12095.raw	Raw
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	FLI12099.raw	Raw
	FLI12101.raw	Raw

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