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Review
. 2023 Feb 9;11(1):30.
doi: 10.3390/diseases11010030.

Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response

Mohammad Rehan Ajmal  1
Affiliations
Review

Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response

Mohammad Rehan Ajmal. Diseases. .

Abstract

Proteins are central to life functions. Alterations in the structure of proteins are reflected in their function. Misfolded proteins and their aggregates present a significant risk to the cell. Cells have a diverse but integrated network of protection mechanisms. Streams of misfolded proteins that cells are continuously exposed to must be continually monitored by an elaborated network of molecular chaperones and protein degradation factors to control and contain protein misfolding problems. Aggregation inhibition properties of small molecules such as polyphenols are important as they possess other beneficial properties such as antioxidative, anti-inflammatory, and pro-autophagic properties and help neuroprotection. A candidate with such desired features is important for any possible treatment development for protein aggregation diseases. There is a need to study the protein misfolding phenomenon so that we can treat some of the worst kinds of human ailments related to protein misfolding and aggregation.

Keywords: aggregation inhibition; amyloid diseases; inflammation; neurodegeneration; protein aggregation.

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Conflict of interest statement

The author declares no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Attainment of native state conformation for a protein by a folding pathway [7,8].
Figure 2
Figure 2
Deviation from the native structure leads to the formation of misfolded intermediates and aggregates [18].
Figure 3
Figure 3
Under certain denaturation conditions, a protein moving into an aggregated state is more energetically favorable than the native state [55].
Figure 4
Figure 4
Methods and instrumentation applied to study amyloid formation [84].
Figure 5
Figure 5
Mechanisms of handling misfolded and aggregated proteins [101].
Figure 6
Figure 6
Therapeutic strategies for protein aggregation diseases [75,119,120].
See this image and copyright information in PMC

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