Patterson Lab
Lab Personnel
- Joseph R. Patterson, PhD, Principal Investigator
- Seth Nelson
Overview
Parkinson’s disease (PD) is a progressive neurodegenerative disorder commonly associated with motor symptoms such as tremor (shaking), rigidity (stiffness), bradykinesia (slowness to initiate movement), and postural instability (impaired balance). A hallmark of PD is the accumulation of alpha-synuclein containing aggregates in dopamine neurons followed by dysfunction and degeneration of these neurons. Diseases where alpha-synuclein aggregates and degeneration follows are classified as “synucleinopathies”.
By the time motor symptoms appear in PD, significant and irreversible neurodegeneration has occurred. As such, understanding what happens early in synucleinopathy is critical to early detection and development of intervention strategies. To study this our lab uses an animal model where lab generated alpha-synuclein fibrils are used to induce aggregation and neurodegeneration in the brain (the preformed fibril or PFF model). Through use of this model, we have begun to identify changes in gene expression in neurons and support cells (microglia and astrocytes) that occur well before the death of the dopamine neurons. This has led to the identification of potential therapeutic targets which we are currently pursuing.
As the PFF model has a well characterized and reproducible time course in our animal model, we have also leveraged it to test the effectiveness of repurposed drugs predicted to be beneficial in PD. These studies have primarily assessed the ability of these treatments to prevent/reduce alpha-synuclein aggregation and dopamine neuron loss.
Experiments in the lab are performed in a highly controlled environment where researchers have control over age, diet, genetic variation/mutation, light cycle, environmental exposures, presence of other diseases/disorders (comorbidities), etc. These features add a level of complexity and as such research is often performed in a vacuum using young, healthy, and genetically identical animals in a stress-free environment with a controlled diet. A focus of our lab is studying the impact of common features of the human condition on synucleinopathy progression. To study these features, we utilize the well characterized and reproducible time course of the alpha-synuclein preformed fibril-induced animal model of synucleinopathy.
One feature we are currently focused on is the effects of advanced age, as aging is the greatest risk factor to developing Parkinson’s disease. To do this we have been assessing the similarities and differences of synucleinopathy in young and old animals. Additionally, as type 2 diabetes has been associated with an increased risk and accelerated Parkinson’s disease progression, we have been examining synucleinopathy severity and progression in an animal model which combines several features of type 2 diabetes with our established synucleinopathy model. Our overall goals in these focuses are to understand how these variables contribute to alpha-synuclein accumulation and neurodegeneration, and determine if there are common pathways that can be targeted with new or repurposed drugs.