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Andrew Arrant, Ph.D.Andrew Arrant, Ph.D.

The American Parkinson Disease Association (APDA) has recently allocated $1.975 million to support groundbreaking research in the field of Parkinson's disease (PD) for the upcoming year, 2023-2024.

APDA's research focus is steadfast, with an emphasis on identifying and supporting early-career researchers to encourage their dedication to PD research and aiding established investigators in pursuing innovative ideas.

The research initiatives to be funded will explore various crucial aspects of PD biology, such as investigating RNA regulation in levodopa-induced dyskinesia, cognitive impairment in PD patients, and the impact of physical activity on Latino/a PD patients.

Additionally, researchers will delve into topics like the structure of mutant LRRK2, SARS-CoV-2-induced damage to dopamine neurons, and more.

Two distinguished assistant professors in the UAB Department of Neurology, Andrew Arrant, Ph.D., and Briana De Miranda, Ph.D., have been selected as recipients in the upcoming 2023-2024 funding year.

Arrant's research investigates how reduced progranulin levels impact a-synuclein aggregation in mouse models, potentially influencing neuronal loss, inflammation, lysosomal dysfunction, and behavioral deficits.

“Mutations in the progranulin gene are a major cause of familial Frontotemporal Dementia and are associated with Dementia with Lewy Bodies (DLB)," said Arrant. "Most of these mutations cause progranulin haploinsufficiency, with mutation carriers having less than half as much progranulin as people without progranulin mutations."

"Other genetic variants of progranulin increase the risk for PD. PD and DLB are characterized by aggregation of α-synuclein in the brain, so we are investigating whether mice with low levels of progranulin are more susceptible to the development of α-synuclein pathology and other PD-like changes".

Briana De Miranda, Ph.D., Briana De Miranda, Ph.D.De Miranda’s research will explore whether inhibiting the specific kinase protein, cyclin-dependent kinase 5 (Cdk5), can shield against the development of Parkinson's disease symptoms induced by environmental exposures associated with an increased risk of PD.

“Dysregulation of the kinase protein Cdk5 has long been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s and Parkinson’s," said De Miranda. "However, we recently found that exposure to the environmental pollutant trichloroethylene (TCE), which is associated with 70% increased risk for PD, specifically elevated Cdk5 activity in neurons."

“This provided an opportunity to test whether pharmacologically or genetically blocking Cdk5 activity could prevent TCE-induced Parkinson’s neurodegeneration using experimental models in my lab.”

Furthermore, we are delighted to share that the UAB Department of Neurology will also continue to receive funding for our APDA Center for Advanced Research, further solidifying our collaborative efforts in the pursuit of innovative solutions for PD.