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Misfolded Proteins Recognition Strategies of E3 Ubiquitin Ligases and Neurodegenerative Diseases

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Abstract

Impairment in the clearance of misfolded proteins by functional proteins leads to various late-onset neurodegenerative diseases. Cell applies a strict quality control mechanism against malfunctioned proteins which may generate cellular proteoxicity. Under proteotoxic insults, cells immediately adopt two major approaches to either refold the misfolded proteinaceous species or degrade the unmanageable candidates. However, the main cellular proteostasis quality control mechanism is not clear. It is therefore important to understand the events and cellular pathways, which are implicated in the clearance of recalcitrant proteins. Ubiquitin proteasome system manages intracellular protein degradation. In this process, E3 ubiquitin ligase enzyme provides specificity for recognition of client proteins. In this review, we summarize various molecular approaches governed by E3 ubiquitin ligases in the degradation of aberrant proteins. A clear understanding of E3 ubiquitin ligases can offer a well tractable therapeutic approach against neurodegenerative diseases.

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Acknowledgments

This work was supported by the Department of Biotechnology, Government of India. AM was supported by Ramalinganswami Fellowship from the Department of Biotechnology, Government of India. The authors would like to thank Mr. Bharat Pareek for his support and management during manuscript preparation.

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  1. Cellular and Molecular Neurobiology Laboratory, Indian Institute of Technology Rajasthan, Jodhpur, 342011, India

    Deepak Chhangani & Amit Mishra

  2. Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon, 122050, India

    Nihar Ranjan Jana

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  1. Deepak Chhangani
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Correspondence to Amit Mishra.

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Chhangani, D., Jana, N.R. & Mishra, A. Misfolded Proteins Recognition Strategies of E3 Ubiquitin Ligases and Neurodegenerative Diseases. Mol Neurobiol 47, 302–312 (2013). https://doi.org/10.1007/s12035-012-8351-0

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