Proteostasis

Proteostasis refers to the regulation of the cellular concentration, synthesis, folding, transport, and breakdown of proteins. The term is a portmanteau of the words "protein" and "homeostasis". Proteostasis is crucial for cell function and survival.

Overview

Proteostasis involves a complex network of biological pathways that control the biogenesis, folding, trafficking and degradation of proteins. This network is known as the proteostasis network and includes the protein synthesis machinery, the protein folding machinery, and the protein degradation machinery.

The proteostasis network is regulated by a set of signaling pathways known as the unfolded protein response (UPR), the heat shock response (HSR), and the oxidative stress response (OSR). These pathways are activated in response to protein misfolding and aggregation, which can lead to cellular dysfunction and disease.

Role in Disease

Disruptions in proteostasis can lead to the accumulation of misfolded and aggregated proteins, which is a hallmark of many diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS).

In these diseases, the proteostasis network is unable to cope with the increased demand for protein folding and degradation, leading to the accumulation of toxic protein aggregates. This suggests that enhancing the capacity of the proteostasis network could be a therapeutic strategy for these diseases.

Therapeutic Strategies

Several therapeutic strategies are being explored to enhance proteostasis, including the use of small molecules that can enhance the capacity of the proteostasis network, the use of gene therapy to increase the expression of proteostasis network components, and the use of protein replacement therapy to replace misfolded or aggregated proteins.

See Also

• Protein folding
• Protein degradation
• Protein synthesis
• Unfolded protein response
• Heat shock response
• Oxidative stress response

References

Proteostasis Resources
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