image: Figure 1. Overview of drivers of GluCer accumulation, which leads to cellular senescence in dopaminergic neurons. Aging, stress, lysosomal dysfunction, decreased levels of GBA, and the regulation of GBA by reactive dopamine have all been shown to lead to the accumulation of glucocerebrosides (GluCer). We have recently shown that the accumulation of GluCer directly drives senescence of dopaminergic (DA) neurons, indicated by lysosomal accumulation, mitochondrial dysfunction, elevated senescence-associated ß-galactosidase, increased p21/p16 expression, and SASP factor upregulation (representative diagrams and images are modified from our previous study [10]).
Credit: 2024 Russo and Riessland
"These findings align with our previous results in dopaminergic neurons in highlighting a central role for lipid accumulation in the senescence of DA neurons."
BUFFALO, NY- August 13, 2024 – A new research perspective was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 14 on July 19, 2024, entitled, “Lipid accumulation drives cellular senescence in dopaminergic neurons.”
As highlighted in the Abstract of this perspective, Parkinson’s disease (PD) is an age-related movement disorder caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the midbrain. However, the underlying causes of this DA neuron loss in PD are unknown, and there are currently no effective treatments to prevent or slow neuronal loss or the progression of related symptoms.
In their perspective, researchers Taylor Russo and Markus Riessland from Stony Brook University found that artificially inducing GluCer accumulation leads to cellular senescence of DA neurons. This suggests that lipid aggregation plays a crucial role in the pathology of PD by driving senescence in these vulnerable neurons.
“Here, we discuss the relevance of the age-related aggregation of lipids as well as the direct functional link between general lipid aggregation, cellular senescence, and inflammaging of DA neurons.”
Additionally, they propose that the expression of a cellular senescence phenotype in the most vulnerable neurons in PD can be triggered by lysosomal impairment and lipid aggregation.
“Importantly, we highlight additional data that perilipin (PLIN2) is significantly upregulated in senescent DA neurons, suggesting an overall enrichment of lipid droplets (LDs) in these cells.”
Continue reading: DOI: https://doi.org/10.18632/aging.206030
Correspondence to: Markus Riessland - markus.riessland@stonybrook.edu
Keywords: lipids, cellular senescence, Parkinson’s disease, glucosylceramides, lysosomes neuroinflammation
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The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)
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Journal
Aging-US
Method of Research
News article
Subject of Research
Cells
Article Title
Lipid accumulation drives cellular senescence in dopaminergic neurons
Article Publication Date
19-Jul-2024
COI Statement
The authors declare no conflicts of interest related to this study.