Project Grant R56NS146375

The National Institute of Neurological Disorders and Stroke awarded the University of Illinois $528,643 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to investigate inhibition of specific kinases in the p38 MAPK pathway module as a potential treatment for genetic forms of amyotrophic lateral sclerosis (ALS).

The project focuses on axonal degeneration, an early pathological event in ALS. Prior research documented deficits in fast axonal transport (FAT)—a cellular process sustaining axonal homeostasis—in nerves from ALS-affected patients and familial ALS (FALS) models. The funded work seeks to elucidate how functionally unrelated FALS-linked proteins including mutant superoxide dismutase 1 (mSOD1) and mutant profilin-1 (mPFN1) elicit FAT deficits by promoting abnormal activation of p38 mitogen-activated protein kinases (MAPK), specifically the p38A isoform. The research uses ex vivo axonal preparations and in vivo models, including SOD1G93A mice, to investigate whether attenuation of p38A signaling prevents or delays spinal cord axon degeneration and to identify axonal proteins undergoing aberrant phosphorylation in the presence of mSOD1, including kinesin-1 and neurofilaments.

Performance occurs in Chicago, Illinois, with a period of performance from September 1, 2026, through August 31, 2027.