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Thus, since several mutations affecting the functional domains of p62 have been identified in patients with ALS and frontotemporal dementia, it has been demonstrated that p62 variants exhibit reduced KEAP1-binding, preventing NRF2 from entering the nucleus and promoting protective genes, and predisposing the cell death upon exposure to ROS [250, 251]

Your hair tends to be a reflection of whats going on in your body

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These substances are often substances produced by the body (metabolites) that cannot be removed properly due to the impaired function of the kidneys

Or you might get a lobectomy (removal of one of your thyroid lobes if just one is cancerous)

It acts there at specific synapses and just covers a small space, and it therefore produces temporally and spatially very precise signalling