The process of protein degradation and clearance of cellular components may be more important in maintaining the nervous system and keeping neurodegeneration at bay than was previously understood, according to two papers to be published online by Nature this week.
Autophagy - protein degradation and recycling of cellular components - is important for the normal growth and development of a cell. Two research teams now show that inhibiting this process in mouse brain cells results in neurodegeneration and early death.
In the first paper, Keiji Tanaka and colleagues create mice with a neural-cell-specific deficiency in the Atg7 gene, which encodes a key enzyme essential for autophagosome formation. These mice exhibited a reduction in coordinated movement, and a massive buildup of proteins and loss of neurons in the cerebral and cerebellar cortices, which led to a premature death 28 weeks after birth.
In the second paper, Noboru Mizushima and colleagues knocked out the Atg5 gene. These mice also developed progressive motor-function impairment and tremors, which were accompanied by the accumulation of cytoplasmic protein-containing inclusion bodies in neurons. Both papers show that the continual clearance of cellular components is essential for maintaining neuronal health and opens new avenues of research to tackle neurodegenerative disease.
Keiji Tanaka (The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan)
Noboru Mizushima (The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan)
(C) Nature press release.
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