University of Georgia has received a USD 1.3 million NIH RF1 grant from the National Institute of Neurological Disorders and Stroke to investigate epitranscriptomic mechanisms driving neuroinflammation in Parkinson's disease, targeting a newly identified role for the m6A demethylase ALKBH5 in microglial activation.
The three-year award, running through April 2029, is led by Anumantha Kanthasamy and Arthi Kanthasamy in the university's Department of Physiology. The project centers on how alpha-synuclein fibrils trigger a proinflammatory cascade in microglia through posttranscriptional regulation of cytokine and chemokine transcripts — a mechanism the investigators implicate via ALKBH5, an enzyme that removes N6-methyladenosine (m6A) modifications from mRNA.
The scientific rationale draws on the team's own proteomic data showing rapid ALKBH5 induction in microglia exposed to alpha-synuclein fibrils, as well as upregulation of the enzyme in animal models of Parkinson's disease and in postmortem human brain tissue from patients with the disease. Their preliminary work further identifies PKCδ-mediated phosphorylation of ALKBH5 as a mechanism controlling its subcellular localization and enzymatic activity, positioning the Fyn-PKCδ-ALKBH5 axis as a candidate therapeutic target. The inclusion of human postmortem tissue distinguishes this award from purely mechanistic preclinical programs and strengthens its translational framing.