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Are heat shock proteins therapeutic target for Parkinson's disease?

Luo GR, Chen S, Le WD - Int. J. Biol. Sci. (2006)

Bottom Line: It is postulated that HSPs may serve as protein folding machinery and work together with ubiquitin-proteasome system (UPS) to assist in decomposing aberrant proteins.In addition, HSPs may possess anti-apoptotic effects and keep the homeostasis of dopaminergic neurons against stress conditions.The critical role of HSPs and recent discovery of some novel HSPs inducers suggest that HSPs may be potential therapeutic targets for PD and other neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Heat shock proteins (HSPs), known as molecular chaperone to assist protein folding, have recently become a research focus in Parkinson's disease (PD) because the pathogenesis of this disease is highlighted by the intracellular protein misfolding and inclusion body formation. The present review will focus on the functions of different HSPs and their protective roles in PD. It is postulated that HSPs may serve as protein folding machinery and work together with ubiquitin-proteasome system (UPS) to assist in decomposing aberrant proteins. Failure of UPS is thought to play a key role in the pathogenesis of PD. In addition, HSPs may possess anti-apoptotic effects and keep the homeostasis of dopaminergic neurons against stress conditions. The critical role of HSPs and recent discovery of some novel HSPs inducers suggest that HSPs may be potential therapeutic targets for PD and other neurodegenerative disorders.

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Related in: MedlinePlus

The Ubiquitin-Proteasome System and the functions of PD associated genes. Parkin works as E3 ligase to help the aberrant protein be poly-ubiquitinated. And UCH-L1 helps hydrolyze the poly-Ub to Ub which can be reused in the next cycle. And when the 26S proteasome is inhibited, HSPs will be induced to compensate the function of protein degradation.
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Figure 2: The Ubiquitin-Proteasome System and the functions of PD associated genes. Parkin works as E3 ligase to help the aberrant protein be poly-ubiquitinated. And UCH-L1 helps hydrolyze the poly-Ub to Ub which can be reused in the next cycle. And when the 26S proteasome is inhibited, HSPs will be induced to compensate the function of protein degradation.

Mentions: The UPS plays a pivotal role in the degradation of short-lived regulatory proteins which are components of cell cycle regulation, cell surface receptors, ion channels modulation, and antigen presentation 56. (Figure 2) It is believed that once the disposal system fails to work, the substances, such as regulatory molecules p53, NFκB, and Bax that promote apoptosis, may accumulate to a high level that is harmful to the cell 57. A hypothesis for the etiology of PD is that subsets of neurons are vulnerable to a failure in proteasome-mediated protein turnover 56. Accumulation of ubiquitin conjugates has been reported in the pathologic lesions of many chronic neurodegenerative diseases, such as the neurofibrillary tangles in AD and brainstem Lewy bodies in PD 55, 56. Inhibition of proteasome activity will sensitize dopaminergic neurons to protein alterations and oxidative stress 58.


Are heat shock proteins therapeutic target for Parkinson's disease?

Luo GR, Chen S, Le WD - Int. J. Biol. Sci. (2006)

The Ubiquitin-Proteasome System and the functions of PD associated genes. Parkin works as E3 ligase to help the aberrant protein be poly-ubiquitinated. And UCH-L1 helps hydrolyze the poly-Ub to Ub which can be reused in the next cycle. And when the 26S proteasome is inhibited, HSPs will be induced to compensate the function of protein degradation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1622889&req=5

Figure 2: The Ubiquitin-Proteasome System and the functions of PD associated genes. Parkin works as E3 ligase to help the aberrant protein be poly-ubiquitinated. And UCH-L1 helps hydrolyze the poly-Ub to Ub which can be reused in the next cycle. And when the 26S proteasome is inhibited, HSPs will be induced to compensate the function of protein degradation.
Mentions: The UPS plays a pivotal role in the degradation of short-lived regulatory proteins which are components of cell cycle regulation, cell surface receptors, ion channels modulation, and antigen presentation 56. (Figure 2) It is believed that once the disposal system fails to work, the substances, such as regulatory molecules p53, NFκB, and Bax that promote apoptosis, may accumulate to a high level that is harmful to the cell 57. A hypothesis for the etiology of PD is that subsets of neurons are vulnerable to a failure in proteasome-mediated protein turnover 56. Accumulation of ubiquitin conjugates has been reported in the pathologic lesions of many chronic neurodegenerative diseases, such as the neurofibrillary tangles in AD and brainstem Lewy bodies in PD 55, 56. Inhibition of proteasome activity will sensitize dopaminergic neurons to protein alterations and oxidative stress 58.

Bottom Line: It is postulated that HSPs may serve as protein folding machinery and work together with ubiquitin-proteasome system (UPS) to assist in decomposing aberrant proteins.In addition, HSPs may possess anti-apoptotic effects and keep the homeostasis of dopaminergic neurons against stress conditions.The critical role of HSPs and recent discovery of some novel HSPs inducers suggest that HSPs may be potential therapeutic targets for PD and other neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
Heat shock proteins (HSPs), known as molecular chaperone to assist protein folding, have recently become a research focus in Parkinson's disease (PD) because the pathogenesis of this disease is highlighted by the intracellular protein misfolding and inclusion body formation. The present review will focus on the functions of different HSPs and their protective roles in PD. It is postulated that HSPs may serve as protein folding machinery and work together with ubiquitin-proteasome system (UPS) to assist in decomposing aberrant proteins. Failure of UPS is thought to play a key role in the pathogenesis of PD. In addition, HSPs may possess anti-apoptotic effects and keep the homeostasis of dopaminergic neurons against stress conditions. The critical role of HSPs and recent discovery of some novel HSPs inducers suggest that HSPs may be potential therapeutic targets for PD and other neurodegenerative disorders.

Show MeSH
Related in: MedlinePlus