Switching on Endogenous Metal Binding Proteins in Parkinson's Disease

Cells
Fleur A McLearyD L Pountney

Abstract

The formation of cytotoxic intracellular protein aggregates is a pathological signature of multiple neurodegenerative diseases. The principle aggregating protein in Parkinson's disease (PD) and atypical Parkinson's diseases is α-synuclein (α-syn), which occurs in neural cytoplasmic inclusions. Several factors have been found to trigger α-syn aggregation, including raised calcium, iron, and copper. Transcriptional inducers have been explored to upregulate expression of endogenous metal-binding proteins as a potential neuroprotective strategy. The vitamin-D analogue, calcipotriol, induced increased expression of the neuronal vitamin D-dependent calcium-binding protein, calbindin-D28k, and this significantly decreased the occurrence of α-syn aggregates in cells with transiently raised intracellular free Ca, thereby increasing viability. More recently, the induction of endogenous expression of the Zn and Cu binding protein, metallothionein, by the glucocorticoid analogue, dexamethasone, gave a specific reduction in Cu-dependent α-syn aggregates. Fe accumulation has long been associated with PD. Intracellularly, Fe is regulated by interactions between the Fe storage protein ferritin and Fe transporters, such as poly(C)-binding prote...Continue Reading

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Citations

Oct 18, 2019·Frontiers in Neuroscience·Dario ValdinocciDean L Pountney
Mar 15, 2020·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Emma LorentzonPernilla Wittung-Stafshede
Dec 15, 2019·Cells·Muhammad Umair, Majid Alfadhel
Jan 14, 2021·Cellular and Molecular Life Sciences : CMLS·Anna CozziSonia Levi
Oct 27, 2020·Frontiers in Neuroinformatics·Vignayanandam Ravindernath Muddapu, V Srinivasa Chakravarthy
Dec 11, 2020·Cells·Ikuko Miyazaki, Masato Asanuma

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Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.