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Can Plant-Made Copper Chaperone for Superoxide Dismutase Heal Early Alzheimer’s Disease?
Abstract: Commercially available medicinal plant extracts such as Ginkgo biloba leaf extract show no consistent pattern of clinical benefit for people with dementia or cognitive impairment, and have been suggested to be toxic to cells at higher doses. However, medicinal plants may contain other more efficient bioactive molecules apart from the well-known flavonoids and terpenoids. Therapeutic recombinant proteins, plant-made copper chaperone for superoxide dismutase (CCS) derived from Ginkgo biloba leaves, may establish and maintain physiologic Cu levels through restoration and modulation of biometal metabolism in organ systems of younger Alzheimer patients (> 50 years). Medications developed from plant-made copper chaperone proteins may delay progression during early disease stages or even be a basis for a possible causal treatment of preclinical stages of Alzheimer’s disease by preventing formation of A β plaques in the brain, a major putative factor involved in Alzheimer’s disease etiopathogenesis.
Keywords: CCS, Ginkgo biloba, SOD, molecular chaperones, key mechanism, recombinant plant-made pharmaceuticals (PMPs), metal ion homeostasis, A β, molecular farming, QPNC-PAGE, NMR.
The dysregulation of biometal (Cu, Zn, Fe) homeostasis and oxidative stress in brain cells have been found to impact on the interaction between metal ions and amyloid β (A β), a major putative factor involved in early Alzheimer’s disease (AD) pathogenesis [1,2]. The regulation of metal ion homeostasis in the cytoplasm is strongly influenced by the copper chaperone for superoxide dismutase (CCS) and Cu,Zn-superoxide dismutase (SOD-1) . The dynamic interplay of properly folded CCS and SOD-1 guarantees that free Cu and Zn ions are being complexed by these metal proteins and do not catalyze oxidation processes of proteins, lipids, DNA or other molecules in the cells . When these physiological complexation mechanisms do not function properly, oxidative stress and dyshomeostasis of Cu and Zn metabolism may give rise to misfolding, accumulation and aggregation of amyloid β peptides . The outcome of these pathological processes may lead to different incurable chronically progressive neurodegenerative diseases such as Alzheimer’s disease [1-3]. Several therapeutic strategies and nearly all medications used or suggested as A β inhibitors, including metal-chelating agents or radical scavengers, at present time, aim at the treatment of AD symptoms only and may either be toxic, lack specificity or have unknown mechanisms of action in vivo [3,4].
The aim of this article is to give a short review on the interaction of metal ions with novel and early herbal compounds derived from Ginkgo biloba, and their possible role in the treatment of early Alzheimer’s disease. Though Ginkgo biloba leaf extracts are generally administered to treat dementia syndroms in older AD patients (> 65 years old), no data is available on possible effects of recombinant plant-made copper chaperones from Ginkgo biloba in younger AD patients (> 50 years old) with preclinical stages of disease.
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- Bernd Kastenholz (Author), 2012, Can Plant-Made Copper Chaperone for Superoxide Dismutase Heal Early Alzheimer’s Disease?, Munich, GRIN Verlag, https://www.grin.com/document/205007