Aberrant autophagy and parkinsonism: does correction rescue from disease progression?
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.
CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226 001, Uttar Pradesh, India.
Abhishek Kumar
AK
Mishra
Mohd Sami
MS
ur Rasheed
Saurabh
S
Shukla
Manish Kumar
MK
Tripathi
Anubhuti
A
Dixit
Mahendra Pratap
MP
Singh
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
D004298:Dopamine