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Oxford-Harrington Rare Disease Scholar Award
Leveraging Exercise to Improve Cognitive Function in Alzheimer's Disease
2021 ADDF-Harrington Scholar
Cognitive function is a serious medical and social challenge affecting an increasingly aging population. Alzheimer's disease (AD) alone affects an estimated 5.5 million Americans, and current drug treatment options are limited. But a new discovery linked to daily exercise holds promise for novel AD treatment.
“Regular physical exercise improves cognitive functions by stimulating adult hippocampal neurogenesis and reducing neuroinflammation,” says Dr. Christiane Wrann. “We traced these effects to irisin, a natural hormone secreted from muscles in response to exercise.”
The irisin hormone, which is the secreted form of FNDC5 (fibronectin-domain III containing 5), offers neuroprotection in aging brain cells, delaying neural degeneration while guarding against obesity, insulin resistance, and nonalcoholic fatty liver disease.
FNDC5, which is expressed in skeletal muscle and the brain, is upregulated in aerobic exercise. Dr. Wrann's preclinical research in mice showed that genetic deletion of irisin impairs cognitive function while an increase improves memory and reduces brain inflammation.
With support from Harrington Discovery Institute and the Alzheimer's Drug Discovery Foundation (ADDF), the Wrann lab is investigating dosing strategies that allow enough irisin to cross the blood-brain barrier to do its work. They will also perform a proof-of-concept/principle study with recombinant irisin in preclinical Alzheimer mouse models.
“Surprisingly, our findings showed that irisin was not acting on neurons, but the astrocytes and microglia that nourish neurons so we can think, move, and breathe,” Dr. Wrann said. “We can't rescue/revive neurons that have died/degenerated, but we believe irisin is a key to extending independent living—and that would be a huge win.”