An intriguing finding in nematode worms suggests that having a little bit of extra fat may help reduce the risk of developing some neurodegenerative diseases, such as Huntington’s, Parkinson’s and Alzheimer’s diseases.

What these illnesses have in common is that they’re caused by abnormal proteins that accummulate in or between brain cells to form plaques, producing damage that causes mental decline and early death.

Huntington’s disease, for example, is caused by aggregating proteins inside brain neurons that ultimately lead to motor dysfunction, personality changes, depression and dementia, usually progressing rapidly after onset in people’s 40s.

These protein aggregates – called Huntington’s aggregates – have been linked to problems with the repair system that nerve cells rely on to fix proteins that fold incorrectly: the cell’s so-called protein folding response. Misfolded proteins can make other proteins fold incorrectly, creating a chain reaction of misfolded proteins that form clumps that the cell can’t deal with.

When researchers perturbed the mitochondria, in a strain of the nematode C. elegans that mimics Huntington’s disease, they saw their worms grow fat. They traced the effect to increased production of a specific type of lipid that, surprisingly, prevented the formation of aggregate proteins. The fat, they found, was required to turn on genes that protected the animals and cells from Huntington’s disease, revealing a new pathway that could be harnessed to treat the disease. The same proved true in human cell lines cultured in a dish.

The researchers subsequently treated worms and human cells with Huntington’s disease with drugs that prevented the cell from sweeping up and storing the lipid, called ceramide, and saw the same protective effect.

Paper: “Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response”

Reprinted from materials provided by the University of California Berkeley.

November 2, 2016