Keeping the importance of cupric Cu in biological function, an elaborate mechanism is set forth by Nature for maintaining Cu homeostasis, which includes a wide array of proteins namely (i) family of Cu bearing proteins, (ii) cuproenzymes, (iii) Cu transporters and (iv) Cu chaperone proteins.
The final straw could be the loss of chaperone proteins, which oversee protein-folding, or a strike by the cellular machinery that transports or breaks down proteins, causing crowding in the cell that foments aggregation.
The article reports on certain aspects of MANFtrafficking inside the cell and its secretion outside the cell, as well as MANF's interactions with other chaperone proteins of the endoplasmic reticulum (ER).
The unfolded protein response maintains a balance between unfolded proteins and chaperones by regulating the rate of transcription and translation of chaperone proteins (David Ron, University of Cambridge, Cambridge, UK).
By better defining the mechanisms linking chaperone proteins to both the tau aggregation and degradation pathways, we can move toward more individualized, effective therapies targeting Alzheimer's and other distinct neurological disorders," said Dickey.