PMID- 29949106
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20200225
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 35
IP  - 1
DP  - 2019 Jan
TI  - Malfunctioning of Chaperone-Mediated Autophagy in Parkinson's Disease: Feats, 
      Constraints, and Flaws of Modulators.
PG  - 260-270
LID - 10.1007/s12640-018-9917-z [doi]
AB  - Homeostatic regulation of class II programmed cell death/autophagy for the 
      degradation and elimination of substandard organelles and defective proteins is 
      decisive for the survival of dopaminergic neurons. Chaperone-mediated autophagy 
      (CMA), one of the most highly dedicated self-sacrificing events, is accountable 
      for the partial elimination of redundant soluble cytoplasmic proteins in 
      Parkinson's disease (PD). CMA is characterized by the selective delivery of 
      superfluous protein containing lysine-phenylalanine-glutamate-arginine-glutamine 
      (KFERQ)/KFERQ-like motif to the lysosome through molecular chaperones, such as 
      heat shock cognate-70 (Hsc-70). KFERQ/KFERQ-like motif present in the poor 
      quality cytoplasmic substrate protein and Hsc-70 complex is recognized by a 
      janitor protein, which is referred to as the lysosome-associated membrane 
      protein-2A (LAMP-2A). This protein is known to facilitate an entry of 
      substrate-chaperone complex in the lumen for hydrolytic cleavage of substrate and 
      elimination of end-products. Impaired CMA is repeatedly blamed for an 
      accumulation of surplus soluble proteins. However, it is still an enigma if CMA 
      is a bonus or curse for PD. Case-control studies and cellular and animal models 
      have deciphered the contribution of impaired CMA in PD. Current article updates 
      the role of CMA in toxicant models and recapitulates the evidences that have 
      highlighted a link between impaired CMA and PD. Although PD is an irreversible 
      happening and CMA is a dual edging phenomenon, it is anticipated that fine-tuning 
      of the latter encounters the former to a certain extent. Besides, the truth, 
      embellishment, and propaganda regarding the issue are also emphasized in the 
      final segment of the article.
FAU - Tripathi, Manish Kumar
AU  - Tripathi MK
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar 
      Pradesh, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 
      226 001, Uttar Pradesh, India.
FAU - Rajput, Charul
AU  - Rajput C
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar 
      Pradesh, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 
      226 001, Uttar Pradesh, India.
FAU - Mishra, Saumya
AU  - Mishra S
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar 
      Pradesh, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 
      226 001, Uttar Pradesh, India.
FAU - Rasheed, Mohd Sami Ur
AU  - Rasheed MSU
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar 
      Pradesh, India.
AD  - Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 
      226 001, Uttar Pradesh, India.
FAU - Singh, Mahendra Pratap
AU  - Singh MP
AUID- ORCID: 0000-0003-1198-6381
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar 
      Pradesh, India. mpsingh@iitr.res.in.
AD  - Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, 
      226 001, Uttar Pradesh, India. mpsingh@iitr.res.in.
LA  - eng
GR  - EMR/2016/005041/Science and Engineering Research Board/
PT  - Journal Article
PT  - Review
DEP - 20180611
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Humans
MH  - Molecular Chaperones/*metabolism
MH  - Parkinsonian Disorders/*metabolism
OTO - NOTNLM
OT  - Chaperone-mediated autophagy
OT  - Parkinsonism
OT  - Parkinson's disease
OT  - Toxicant models
EDAT- 2018/06/28 06:00
MHDA- 2019/03/21 06:00
CRDT- 2018/06/28 06:00
PHST- 2018/03/20 00:00 [received]
PHST- 2018/05/25 00:00 [accepted]
PHST- 2018/05/22 00:00 [revised]
PHST- 2018/06/28 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/06/28 06:00 [entrez]
AID - 10.1007/s12640-018-9917-z [pii]
AID - 10.1007/s12640-018-9917-z [doi]
PST - ppublish
SO  - Neurotox Res. 2019 Jan;35(1):260-270. doi: 10.1007/s12640-018-9917-z. Epub 2018 
      Jun 11.