Cell type-specific lipid storage changes in Parkinson’s disease patient brains are recapitulated by experimental glycolipid disturbance
Abstract
Recently, the field of Parkinson’s disease biology has shifted attention away from pure proteinotoxic hypotheses to emphasize primary cellular insults, including glycolipid disturbances. In this work, dopaminergic neurons in the Parkinson’s disease-vulnerable region of substantia nigra were found to accumulate neutral lipids, whereas in the same tissues, astrocytes have reduced lipid content, and resident microglia (a form of brain macrophage) show overall accumulation of lipids associated with inflammation. These changes were reproduced experimentally by blocking a specific lysosomal hydrolase in mice, generating a glycolipid accumulation in the animals. Based on these findings, it is reasonable to propose that restoring lipid homeostasis between neurons, astrocytes, and microglia could potentially influence PD pathogenesis and disease progression.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 15, 2020
- Source ID
- 10.1073/pnas.2003021117
Entities
People
- Jonathan R Honey
- Oeystein Roed Brekk
- Ole Isacson
- Penelope J. Hallett
- Seungil Lee
Organizations
- Harvard Medical School
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging
- United States Department of Defense