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Exploring the Role of Autophagy Dysfunction in Neurodegenerative Disorders

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Abstract

Autophagy is a catabolic pathway by which misfolded proteins or damaged organelles are engulfed by autophagosomes and then transported to lysosomes for degradation. Recently, a great improvement has been done to explain the molecular mechanisms and roles of autophagy in several important cellular metabolic processes. Besides being a vital clearance pathway or a cell survival pathway in response to different stresses, autophagy dysfunction, either upregulated or down-regulated, has been suggested to be linked with numerous neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis. Impairment at different stages of autophagy results in the formation of large protein aggregates and damaged organelles, which leads to the onset and progression of different neurodegenerative disorders. This article elucidates the recent progress about the role of autophagy in neurodegenerative disorders and explains how autophagy dysfunction is linked with the pathogenesis of such disorders as well as the novel potential autophagy-associated therapies for treating them.

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Acknowledgements

The authors would like to thank Chitkara University, Punjab, India for providing the basic facilities for the completion of this article.

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  1. Tarapati Rana and Tapan Behl are authors with equal contributions.

Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Tarapati Rana, Tapan Behl, Aayush Sehgal & Sukhbir Singh

  2. Government Pharmacy College, Seraj, Mandi, Himachal Pradesh, India

    Tarapati Rana

  3. Government College of Pharmacy, Rohru, Distt. Shimla, Himachal Pradesh, India

    Vineet Mehta

  4. Amity Institute of Pharmacy, Amity University, Haryana, India

    Saurabh Bhatia

  5. Natural & Medical Sciences Research Centre, University of Nizwa, Nizwa, Oman

    Saurabh Bhatia & Ahmed Al-Harrasi

  6. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona Bungau

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Highlights

• Autophagy is an evolutionary conserved cellular process and is crucial for maintaining cellular homeostasis.

• Autophagy performs an essential role in the pathophysiology of several neurodegenerative disorders.

• Autophagy is regulated by important nutrient-sensing pathways including the mTORC1 and AMPK.

• Autophagy is a potential therapeutic target to ameliorate neurodegenerative disorders.

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Rana, T., Behl, T., Sehgal, A. et al. Exploring the Role of Autophagy Dysfunction in Neurodegenerative Disorders. Mol Neurobiol 58, 4886–4905 (2021). https://doi.org/10.1007/s12035-021-02472-0

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  • DOI: https://doi.org/10.1007/s12035-021-02472-0

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