Evidence map›Paper›PMID 29686608›Full record

ArticleFrontiers in molecular neuroscience2018

Modulation of Autophagy by a Small Molecule Inverse Agonist of ERRα Is Neuroprotective.

S N Suresh, Aravinda K Chavalmane, Malini Pillai, Veena Ammanathan, D J Vidyadhara, Haorei Yarreiphang, Shashank Rai, Abhik Paul, James P Clement, Phalguni A Alladi and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in molecular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

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  18. Selective autophagy as a therapeutic target for neurological diseases.Cellular and molecular life sciences : CMLS · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

S N SureshMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Aravinda K ChavalmaneMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Malini PillaiMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Veena AmmanathanMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
D J VidyadharaDepartment of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Haorei YarreiphangDepartment of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Shashank RaiMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Abhik PaulNeuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
James P ClementNeuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Phalguni A AlladiDepartment of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Ravi ManjithayaMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Jawaharlal Nehru Centre for Advanced Scientific Research · INNational Institute of Mental Health and Neurosciences · IN

Funding

Wellcome Trust
6 · The paper itself

Abstract

Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, are lacking. Here, we report and describe the role of Estrogen Related Receptor α (ERRα, HUGO Gene Nomenclature ESRRA), new molecular player of aggrephagy, in keeping autophagy flux in check by inhibiting autophagosome formation. A screen for small molecule modulators for aggrephagy identified ERRα inverse agonist XCT 790, that cleared α-synuclein aggregates in an autophagy dependent, but mammalian target of rapamycin (MTOR) independent manner. XCT 790 modulates autophagosome formation in an ERRα dependent manner as validated by siRNA mediated knockdown and over expression approaches. We show that, in a basal state, ERRα is localized on to the autophagosomes and upon autophagy induction by XCT 790, this localization is lost and is accompanied with an increase in autophagosome biogenesis. In a preclinical mouse model of Parkinson's disease (PD), XCT 790 exerted neuroprotective effects in the dopaminergic neurons of nigra by inducing autophagy to clear toxic protein aggregates and, in addition, ameliorated motor co-ordination deficits. Using a chemical biology approach, we unrevealed the role of ERRα in regulating autophagy and can be therapeutic target for neurodegeneration.

Indexed as

autophagyestrogen related receptor αmTOR independent modulatorneuroprotectionParkinson’s diseasesmall molecule screenXCT 790

Identifiers

PMID29686608
PMCPMC5900053
OpenAlexW2796928664

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.