Muscle degeneration, the most prevalent cause of frailty in hereditary diseases and aging, could be caused by a deficiency in one key enzyme in a lipid biosynthesis pathway. Researchers at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences characterize how the enzyme PCYT2 affects muscle health in disease and aging in laboratory mouse models. The findings are published in Nature Metabolism.
"This assumption prompted me to selectively deplete PCYT2 in muscle tissues of animal models and study the outcome. In parallel, clinicians reported patient cases of mutations affecting PCYT2. The patients presented a condition called complex hereditary spastic paraplegia, a severe, multi-symptomatic disease characterized by leg muscle weakness, stiffness, and muscle wasting that worsened with time.
Muscle membrane-derived Giant Plasma Membrane Vesicles . These isolated large membrane units, coupled with advanced microscopy applications, enabled a close analysis of the architecture of the otherwise difficult-to-study cell membrane lipid bilayer, giving insight into an unknown pathological mechanism of a recently discovered, severe human inherited disease. Credit: ©Cikes/IMBA
"This prompted us to think that there must be an additional mechanism driving the pathology," says Cikes. Indeed, the team showed that the organization of the cell membrane lipid bilayer played an additional role."This represents a novel pathophysiological mechanism that might also be present in other lipid-related disorders," says Cikes.
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