Abstract
Proper folding to attain a defined three-dimensional structure is a prerequisite for the functionality of a protein. Improper folding that eventually leads to formation of protein aggregates is a hallmark of several neurodegenerative disorders. Loss of protein homeostasis triggered by cellular stress conditions is a major contributing factor for the formation of these toxic aggregates. A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis. Expanding the body of evidence highlights the role of chaperones as central mediators in the formation, de-aggregation and degradation of the aggregates. Altered expression and function of chaperones is associated with many neurodegenerative diseases including Parkinson’s disease. Several studies indicate that chaperones are at the center of the cause and effect cycle of this disease. An overview of the various chaperones that are associated with homeostasis of Parkinson’s disease-related proteins and their role in pathogenicity will be discussed in this review.
Highlights
Progressive loss of neurons is the most important characteristic of age-associated neurodegenerative diseases [1]
We provide an overview of chaperones involved in the proteostasis and regulation of major Parkinson’s disease (PD) associated proteins (Table 1)
Research till confirms that PD is not a single factor disease but has multiple factors associated to it and, at the same time, that the interactions between environmental factors and the Research till confirms that PD is not a single factor disease but has multiple factors associated to it and, at the same time, that the interactions between environmental factors and the genetic makeup of the person is very crucial. It is an age-associated neurodegenerative disorder and is majorly characterized by loss of proteostasis that eventually results in accumulation of toxic protein aggregates
Summary
Progressive loss of neurons is the most important characteristic of age-associated neurodegenerative diseases [1]. Overexpression of TorsinA, HDJ-1, HDJ-2 and Hsp resulted in the inhibition of α-synuclein aggregation in brain cells of PD patients [42] Another neuronal chaperone, proSAAS, was reported to inhibit the formation of α-synuclein fibrils in humans [43]. A member of the J domain-containing family of proteins interacts with the N-terminus of Hsp and functions as its co-chaperone This interaction leads to enhanced ATP hydrolysis and formation of the more active ADP-bound form of Hsp70 [10]. Overexpression of α-synuclein and inhibition of CMA in neuronal cell types led to increased accumulation of soluble high molecular weight forms of the protein [98,99]. Degradation of Lamp2A and increased aggregation of α-synuclein was observed in cells deficient of DJ-1 [104]
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