Skip to main content

Senescence in Parkinson’s Disease and Related Disorders

Study Rationale:
While aging is the greatest risk factor for development of Parkinson’s disease (PD), how aging promotes PD is not fully understood. Examining the role of cellular senescence (deterioration of function), a major driver of aging, in PD represents a completely novel approach to understanding disease pathophysiology and may lead to new therapeutic approaches.

Senescence and PD-linked gene mutations have reciprocal pathological interactions where (i) senescence causes PD-relevant neuropathology; (ii) PD-linked mutant genes (alpha-synuclein, LRRK2, Vps35) cause premature senescence; and (iii) senescence participates in neuropathology caused by PD-linked genes.

Study Design:
First, we will use novel mouse models of premature senescence to test whether premature senescence in specific cell types causes PD-like neuropathology. Second, we will combine mouse models of senescence and familial PD to test whether senescence participates in neuropathology caused by mutant PD-linked genes. Specifically, we will determine if pathology in a PD mouse model causes premature senescence and whether removing senescent cells from brain can prevent PD pathology.  Finally, we will perform gene expression analysis of PD brains and mouse brains, at a single-cell level, to gain high-resolution insights about cellular processes that link aging and PD pathology.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our results will support the use of senolytics (drugs that selectively kill senescent cells and are currently in Phase II clinical trials) as novel disease-modifying therapies for PD. In addition, our studies may identify new biomarkers of senescence in PD.

Next Steps for Development:
Because senolytics are in Phase II human trials for other indications, they could be applied to PD cases rapidly. Further, efforts can be made to screen for and develop additional senolytic compounds.


  • Michael K. Lee, PhD

    Minneapolis, MN United States

  • Jose Bras, PhD

    Grand Rapids, MI United States

  • Darren J. Moore, PhD

    Grand Rapids, MI United States

  • Laura Niedernhofer, MD, PhD

    Minneapolis, MN United States

Discover More Grants

Search by Related Keywords

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.