The Drp1 pathway may lead to the development of more effective treatments for Alzheimer’s disease
In Science Advances, a peer-reviewed journal, a number of researchers with the Case Western Reserve University uncovered a new pathway that may provide more effective therapeutic options for Alzheimer’s disease.
Referred to as Drp1-HK1-NLRP3, this pathway disrupts the normal function of brain cells, often leading to dysfunction or even elimination of myelin-producing cells, often associated with Alzheimer’s disease.
“In the present study, aberrant Drp1 activation was a primary signal that disturbed the glycolytic homeostasis of mature oligodendrocytes (OLs) in Alzheimer’s disease (AD), triggering sequential inflammatory damage and subsequent white matter loss and axonal degeneration,” the findings read.
“These findings were further corroborated by our results that showed that the mature OL-specific heterozygous knockout of Drp1 corrected the HK1-mediated glycolytic defect in mature OLs, reduced NLRP3 inflammasome activation, attenuated the loss of myelin and axons, and improved cognitive performance in AD mice,” researchers also stated.
As a whole, the study provided a unique insight into white matter degeneration among patients with Alzheimer’s, which has resulted in a new focus for potential therapeutic implications.
“Our findings may also provide insights into where and how this shift in glucose metabolism occurs in AD. Future studies on the lactate shuttle between neurons and OLs via the Drp1-HK1 axis may warrant a better understanding of the mechanism that underlies the blockade of neuronal glucose uptake in AD,” according to researchers.