Protein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates’ formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where ~30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dissagregation activity is catalysed by the stress-responsive ER molecular chaperone – BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.
This blog reports new ideas and work on mind, brain, behavior, psychology, and politics - as well as random curious stuff
Monday, May 16, 2022
How stress might help reduce dementia and alzheimer’s.
The post today (my 80th birthday) points to experimental results relevant to my interest in not losing my marbles anytime soon. Fauzia points to work by Avezov and collaborators (open source) showing that the accumulation of aggregates of misfolded proteins in the endoplasmic reticulum of brain cells that is associated with dementia and Alzheimer's can be reversed by stressing cells with chemicals or heat, activating molecular chaperones that in turn untangle or remove protein aggregates. How much stress is just enough, but not to much, isn't clear. The abstract of the work:
Posted by Deric Bownds at 1:40 PM
Blog Categories: aging, brain plasticity, fear/anxiety/stress
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