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However, emerging data suggest that these effects on expression of muscle PPAR family members in the ERKO mouse may be mediated by indirect action resulting from ER deletion in other metabolic tissues

"Brain glutathione levels -- a novel biomarker for mild cognitive impairment and Alzheimer's disease." Biol Psychiatry

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This idea is supported by other neurodegenerative diseases experiencing severe localized copper deficiency, such as the motor neurons of ALS patients (Hilton et al., 2024), PD patients with up to 50% reduction of copper seen in the substantia nigra (Bisaglia and Bubacco, 2020), brain copper reductions in prion diseases (Sorenson, 2001), and notably Menkes disease which is characterized by an X-linked defect in copper transporting ATP7-A gene that leads to severe systemic copper deficiency and progressive neurodegeneration (Tmer and Mller, 2010)