Researchers have discovered that the skeleton surrounding the nucleus of brain cells is dysfunctional in Alzheimer’s disease patients, which could lead to neuronal death. The study, “Lamin Dysfunction Mediates Neurodegeneration in Tauopathies,” was published in Current Biology.
The lamin nucleoskeleton that surrounds the nucleus of cells is important in the maintenance of nuclear organization, primarily the anchoring of heterochromatin (regions of tightly-packed DNA) to the nuclear envelope and maintenance of the genome’s architecture. In previous research, Dr. Bess Frost and colleagues reported that widespread relaxation of heterochromatin, a consequence of lamin dysfunction, was observed in several tauopathies, diseases like Alzheimer’s that are characterized by aggregates of phosphorylated tau protein in the brain.
Researchers now demonstrate that lamin dysfunction promotes heterochromatin relaxation and neuronal death. Moreover, such dysfunction has a direct causative role in neurotoxicity, as genetic manipulation of lamin led to significant modification of neurodegeneration in vivo. These findings, made on fruit flies, were also verified in post-mortem brain tissue, from donated brains with Alzheimer’s disease. Such observations provide strong evidence that lamin dysfunction is conserved in human tauopathies, diseases that may be laminopathies. The research also uncovers new pathways to study not only disease mechanisms but also new therapeutic avenues to treat Alzheimer’s.
Frost, now establishing her laboratory at the University of Texas Health Science Center’s Barshop Institute for Longevity and Aging Studies, encouraged people to consider brain donation as a way to foster neuroscience research. “Human brain donation is a very critical part of this work,” Frost said in a news release. “It was important to show that what we found in the fly is really relevant to human disease.” Last September, the Health Science Center announced the establishment of a tissue biorepository at the Biggs Institute for Alzheimer and Neurodegenerative Diseases.