Andrew Arrant, PhD
Name of Institution:
University of Alabama at Birmingham, Birmingham, AL
Investigating the role of progranulin in synucleinopathy
Dr. Andrew Arrant is Assistant Professor of Neurology at the Heersink School of Medicine, University of Alabama at Birmingham. He holds a PhD in Pharmacology from Duke University and completed postdoctoral training at the University of Alabama at Birmingham. Dr. Arrant’s research interests center around the cellular mechanisms underlying cognitive and functional deficits in neurodegeneration and aging. His lab focuses on progranulin, a secreted protein linked genetically to Frontotemporal Dementia (FTD), Parkinson’s disease (PD), Dementia with Lewy bodies (DLB), and Alzheimer’s disease (AD). The lab is investigating how progranulin protects against neurodegeneration and how its loss contributes to the development of neurodegenerative pathology.
To determine if progranulin insufficiency promotes a-synuclein aggregation, and if progranulin insufficiency worsens neuronal loss, inflammation, lysosomal dysfunction, and behavioral deficits associated with a-synuclein aggregation.
Mutations in the progranulin gene (GRN) that reduce progranulin levels cause FTD and are associated with DLB. GRN is also genetically associated with the risk of developing PD. Patients with PD or DLB develop aggregates of a-synuclein in the brain. In a mouse model of a-synuclein aggregation, these aggregates are associated with loss of neurons and abnormal behavior. The goal of this project is to determine if mice with low levels of progranulin are more susceptible to a-synuclein aggregation or associated problems, including neuronal loss, inflammation, lysosomal dysfunction, and behavioral deficits such as abnormal social behavior and impaired movement.
Experimental a-synuclein aggregates (fibrils) can be created in test tubes and injected into mouse brains, leading to a-synuclein aggregation in neurons. Mice with varying progranulin levels (normal, low, or none) will receive these injections, and the researchers will evaluate whether mice with reduced progranulin show more severe a-synuclein aggregation, neuronal loss, inflammation, lysosomal dysfunction, or behavioral deficits than those with normal progranulin levels.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Successful results from these experiments would demonstrate that low progranulin levels contribute to the formation of a-synuclein aggregates and the related problems they cause. This finding would support the testing of therapies designed to boost progranulin levels as a potential treatment for a-synuclein aggregation and neurodegeneration in PD and DLB. Currently, progranulin-boosting treatments are being tested in clinical trials for FTD, offering a promising avenue for potentially novel treatments for PD and DLB.