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Aberrant Autophagy and Parkinsonism: Does Correction Rescue from Disease Progression?

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Abstract

Information generated from animal models, genome sequencing, and high-throughput technologies provide valuable sequence of events to understand the Parkinson’s disease (PD) pathogenesis. A dynamic equilibrium between biosynthesis and biodegradation of sub-cellular components by ubiquitin proteasome system and autophagy is found to be responsible for sustaining the homeostasis of tyrosine hydroxylase-positive neurons. Autophagy degrades and eliminates α-synuclein, Parkin, ubiquitin, etc., proteins along with damaged cellular components to maintain the homeostasis of the nigrostriatal dopaminergic neurons. Aberrant type II apoptosis is widely implicated in dopaminergic neurodegeneration leading to PD. The current article reviews the elementary role of autophagy in the degradation and elimination of superfluous and aggregated proteins and impaired mitochondria. The article also recapitulates the information, which implicated the role of aberrant autophagy in toxin-induced Parkinsonism. Moreover, the review sheds light on whether or not targeting the defective autophagy could reinstate the normal functioning of dopaminergic neurons, which could ultimately rescue from PD pathogenesis.

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Acknowledgments

Authors acknowledge the Council of Scientific and Industrial Research (CSIR), Department of Science and Technology, Department of Biotechnology, and University Grants Commission, New Delhi, India for providing financial assistance to Abhishek Kumar Mishra, Mohd Sami ur Rasheed, Manish Kumar Tripathi, and Anubhuti Dixit, respectively, in the form of fellowship. The financial support from the CSIR in the form of a network program “Neurodegenerative Diseases: Causes and Corrections (BSC0115: miND)” is gratefully acknowledged. The CSIR-IITR communication number of this article is 3,207.

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Authors do not have any conflicts of interest.

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  1. CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226 001, Uttar Pradesh, India

    Abhishek Kumar Mishra, Mohd Sami ur Rasheed, Saurabh Shukla, Manish Kumar Tripathi, Anubhuti Dixit & Mahendra Pratap Singh

  2. Academy of Scientific and Innovative Research, New Delhi, India

    Abhishek Kumar Mishra, Mohd Sami ur Rasheed, Manish Kumar Tripathi & Mahendra Pratap Singh

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  1. Abhishek Kumar Mishra
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Correspondence to Mahendra Pratap Singh.

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Mishra, A.K., ur Rasheed, M.S., Shukla, S. et al. Aberrant Autophagy and Parkinsonism: Does Correction Rescue from Disease Progression?. Mol Neurobiol 51, 893–908 (2015). https://doi.org/10.1007/s12035-014-8744-3

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