Scientists from Baylor College of Medicine and the Ian and Dan Duncan Institute for Neurological Research (USA) have uncovered the mechanism of Lou Gehrig's disease, which the theoretical physicist Stephen Hawking suffered from. It turned out that the mutant protein ubiquilin ceases to regulate the functioning of lysosomes, the components of the cell responsible for the processing of metabolic waste. This was reported in the MedicalXpress press release.
The researchers conducted experiments using fruit flies as model organisms, which lacked a functional version of the gene encoding ubiquiline. The mutant insects showed signs of age-related neurodegeneration, including impaired activity of nerve cells, their death, and the accumulation of damaged lysosomes.
It turned out that defective ubiquiline promotes dysfunction of the proteasome - a protein complex that gets rid of cellular debris - and interferes with autophagy, in which unnecessary cell components are also destroyed. In autophagy, vesicles (cellular vesicles) called autophagosomes take up damaged proteins. Then the vesicles fuse with lysosomes, the acidic environment of which activates enzymes that decompose waste. However, in the presence of mutant ubiquilin, the environment in the lysosomes is not acidic enough.
Scientists plan to test whether the same mechanism is at work in humans. Then the progression of amyotrophic lateral sclerosis can be slowed down by restoring the acidity of the lysosomes.
Amyotrophic lateral sclerosis is an incurable neurodegenerative disease in which the nerve cells of the motor cortex of the brain and motor neurons are damaged. The result is paralysis and muscle atrophy. Patients die from a respiratory tract infection or cessation of the functioning of the respiratory muscles.