Federal Project Grant Award Summary

Brigham & Women's Hospital Inc., through its Department of Faulkner Pathology in Boston, Massachusetts, received a $557,883 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The award was obligated on May 1, 2026, with a completion date of April 30, 2031. This five-year research initiative investigates the pathogenic mechanisms underlying leucine-rich repeat kinase 2 (LRRK2) mutations, which are linked to familial and idiopathic Parkinson's disease, dementia with Lewy bodies, and tauopathies.

The research project examines whether mitochondrial and autophagy-lysosomal dysfunction underlies LRRK2-dependent dopaminergic neuronal survival through both cell-autonomous and non-cell-autonomous mechanisms. The study employs physiologically relevant knockin mouse alleles to assess the impact of two critical LRRK2 mutations (R1441C and G2019S) on dopaminergic neuron degeneration in aging brains, shifting focus beyond the conventional kinase-activity hypothesis to explore broader functional domains of LRRK2. The research represents a multidisciplinary approach to understanding complex neurodegeneration pathways and has potential implications for therapeutic development in neurodegenerative disease treatment.