Molecular Association of Glia Maturation Factor with the Autophagic Machinery in Rat Dopaminergic Neurons: a Role for Endoplasmic Reticulum Stress and MAPK Activation

Molecular Neurobiology
Govindhasamy Pushpavathi SelvakumarAsgar Zaheer

Abstract

Parkinson's disease (PD) is one of the several neurodegenerative diseases where accumulation of aggregated proteins like α-synuclein occurs. Dysfunction in autophagy leading to this protein build-up and subsequent dopaminergic neurodegeneration may be one of the causes of PD. The mechanisms that impair autophagy remain poorly understood. 1-Methyl-4-phenylpiridium ion (MPP+) is a neurotoxin that induces experimental PD in vitro. Our studies have shown that glia maturation factor (GMF), a brain-localized inflammatory protein, induces dopaminergic neurodegeneration in PD and that suppression of GMF prevents MPP+-induced loss of dopaminergic neurons. In the present study, we demonstrate a molecular action of GMF on the autophagic machinery resulting in dopaminergic neuronal loss and propose GMF-mediated autophagic dysfunction as one of the contributing factors in PD progression. Using dopaminergic N27 neurons, primary neurons from wild type (WT), and GMF-deficient (GMF-KO) mice, we show that GMF and MPP+ enhanced expression of MAPKs increased the mammalian target of rapamycin (mTOR) activation and endoplasmic reticulum stress markers such as phospho-eukaryotic translation initiation factor 2 alpha kinase 3 (p-PERK) and inositol-req...Continue Reading

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Citations

Apr 24, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Sudhanshu P RaikwarAsgar Zaheer
Jun 23, 2020·Experimental Neurobiology·Govindhasamy Pushpavathi SelvakumarAsgar Zaheer

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Datasets Mentioned

BETA
GMF

Methods Mentioned

BETA
protein folding
protein assay
enzyme-linked immunosorbent assay
ELISA
Nuclear Translocation

Software Mentioned

GraphPad prism -
ChemiDoc
ImageJ
GraphPad prism - 7
- It2 system
GraphPad InStat
It

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