Molecular Chaperones Research Paper

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Molecular chaperones are the major chaperone group and are also called heat shock proteins (HSPs). They are highly conserved proteins, meaning that they have remained unchanged for a long time in different species. The expression of the HSPs is increased by stress conditions like, for instance, increased temperature. There are several chaperone families that are classified based on their molecular weight. This essay will concentrate on HSP70, HSP90, HSP60 and HSP100, but there are some other types of molecular chaperones as well. HSP70 and HSP90 are the most abundant chaperones in the cells, which makes them the main chaperone family in eukaryotes, that is, in all other organisms except for bacteria and archaea. They have many interaction sites …show more content…
One of them is the use of small molecular chaperones that are divided into chemical chaperones and pharmacological chaperones. Small molecular chaperones are, as their name indicates, small compounds that by counteracting protein aggregate formation promote correct protein folding and stabilization. The chemical chaperones create an environment that favors correct folding of proteins and decreases the amount of unproductive interactions between proteins. Examples of chemical chaperones are molecules called trehalose and mannitol. Trehalose treatment has been tested on rat models of PD, where oral ingestion of it was shown to alleviate both behavioral impairments and the neurochemical pathology. Mannitol has been tested on Drosophila and mouse PD models, and has been shown to reduce the formation of α-synuclein aggregates, which again seems to correct the behavioral impairments associated with PD. Pharmacological chaperones affect the conformation and stability of the substrate protein by binding directly to it. Pharmacological chaperones can cross the blood-brain barrier and have been shown to reduce α-synuclein aggregation. The blood-brain barrier protects the brain from many pathogens, but also inhibits beneficial drugs from entering the brain. Therefore, it is important in clinical treatment that the drug has the ability to cross it. However, high doses of both pharmacological and chemical …show more content…
One such inhibitor is geldanamycin (GA). GA increases the expression of HSP70 by inhibiting the interaction between HSP90 and HSF1. GA treatment in animal models of some other neurodegenerative diseases, such as Huntington’s disease and amyotrophic lateral sclerosis (ALS), has given promising results. Unfortunately, there are several problems with the use of GA. It penetrates the blood-brain barrier poorly and its solubility is weak. In addition to this, it is also toxic. There are similar problems with other GA analogues which appear to be harmful to the liver. One promising HSP90 inhibitor has been found, this being the SNX compounds. They increase the expression of HSP70, but in contrast to the other HSP90 inhibitors mentioned before, they have a good blood-brain barrier permeability and trials with PD rat models have given promising results. SNX can be taken orally, which makes it an even more appealing form of

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