Study Rationale:
Aging is the strongest risk factor for Parkinson’s disease, yet the biological reasons behind this connection remain unclear. Our recent findings suggest that several key aging-related genes may directly regulate alpha-synuclein, the protein that clumps in the brains of people with Parkinson’s. These genes normally protect brain cells by maintaining energy balance, reducing inflammation, and repairing damage. When they become dysregulated, neurons may lose resilience and become more vulnerable to degeneration. Understanding how these genes are expressed in people with Parkinson’s may reveal new clues about the relationship between aging and Parkinson’s disease.
Hypothesis:
We hypothesize that aging-related genes are significantly repressed in Parkinson’s disease and that this reduced activity disrupts the normal control of alpha-synuclein (SNCA) and tau (MAPT). This breakdown may accelerate the cellular damage that leads to PD symptoms and progression.
Study Design:
Our team will analyze extensive brain data from people with and without Parkinson’s. This includes both bulk and single-cell RNA sequencing data that reveal how genes are expressed and network in specific brain regions and cell types, such as dopamine-producing neurons and glial cells. We will identify which aging-related genes are dysregulated in PD, determine how they interact with alpha-synuclein and tau, and assess whether variants in these genes are associated with modified disease progression. This integrated approach combines molecular biology with advanced computational analysis to uncover new biological drivers of PD.
Impact on Diagnosis/Treatment of Parkinson’s disease:
By identifying which aging-related genes regulate alpha-synuclein and tau in Parkinson’s, this study will advance our understanding of why Parkinson’s happens and may uncover novel biomarkers and therapeutic targets that strengthen natural brain defenses, slow symptom progression, and potentially delay disease onset.
Next Steps for Development:
If our results confirm a correlation between aging-related genes and Parkinson’s disease, we will test whether restoring their activity in cellular models of Parkinson’s disease can prevent or reverse neurodegeneration. These experiments will directly guide the design of next-generation therapies targeting the root causes of Parkinson’s disease.