Properly folded, functional proteins are essential for cell health. Cells sustain protein homeostasis, or proteostasis, via protein quality control (PQC) mechanisms. It is currently hypothesized that a breakdown in proteostasis during ageing leads to the accumulation of protein aggregates in the cell and disease. Sequestration of misfolded proteins into PQC compartments represents one branch of the PQC network. In neurodegenerative diseases, certain proteins form abnormal protein deposits. Which PQC compartments house misfolded proteins associated with neurodegenerative diseases is still being investigated. It remains unclear if sequestration of these misfolded proteins is toxic or protective to the cell. Here, we review the current knowledge on various PQC compartments that form in the cell, the kinds of protein aggregates found in neurodegenerative diseases, and what is known about their sequestration. Understanding how protein sequestration occurs can shed light on why aggregates are toxic to the cell and are linked to neurodegenerative diseases like Huntington's, Alzheimer's, and Parkinson's diseases.
The flower represents the Drosophila testis niche with the hub cells at the center. Each petal of the flower represents Germline stem cells (GSCs) with a large and a smaller purple circle representing centromere; green rays representing stronger centromeres preferentially attach to the niche. Red and green caterpillars represent sister chromatids in prometaphase with separable old and new H3 in GSCs. Further, large butterflies closer to the flower represent prometaphase GSCs with a red wing vs a green wing representing non-overlapping old and new H3. Small orange butterflies away from the flower represent prophase gonialblast cells with overlapping old and new H3 signals. The background is from coiled sperm from the fly testis. Cover art generated by Professor Tim Phelps.
Spatial sequestration of misfolded proteins in neurodegenerative diseases
Sarah Rolli, Emily Mitchell Sontag; Spatial sequestration of misfolded proteins in neurodegenerative diseases. Biochem Soc Trans 29 April 2022; 50 (2): 759–771. doi: https://doi.org/10.1042/BST20210862
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