Evidence map›Paper›PMID 37289385›Full record

ArticleMolecular neurobiology2023

Presence of Extracellular Alpha-Synuclein Aggregates Trigger Astrocytic Degeneration Through Enhanced Membrane Rigidity and Deregulation of Store-Operated Calcium Entry (SOCE) into the Endoplasmic Reticulum.

Aishwarya Raj, Roon Banerjee, Rashmi Santhoshkumar, Chandrasekhar Sagar, Indrani Datta

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
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

5 authors at 1 institution in 1 country.

Aishwarya RajDepartment of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, 560029, Karnataka, India.
Roon BanerjeeDepartment of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, 560029, Karnataka, India.
Rashmi SanthoshkumarDepartment of Neuropathology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, 560029, Karnataka, India.
Chandrasekhar SagarDepartment of Neuropathology, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, 560029, Karnataka, India.
Indrani DattaDepartment of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Bengaluru, 560029, Karnataka, India. indranidatta.nimhans@gmail.com.ORCID http://orcid.org/0000-0001-8864-473X
National Institute of Mental Health and Neurosciences · IN

Funding

Department of Biotechnology, Ministry of Science and Technology, India BT/PR21526/MED/122/49/2016
6 · The paper itself

Abstract

α-Synuclein has a critical role in Parkinson's disease, but the mechanism of how extracellular α-synuclein aggregates lead to astrocytic degeneration remains unknown. Our recent study in astrocytes highlighted that α-synuclein aggregates undergo lower endocytosis than the monomeric-form, even while displaying a higher impact on glutathione-machinery and glutamate-metabolism under sublethal conditions. As optimal intracellular calcium levels are essential for these functions, we aimed to study the effect of extracellular α-synuclein aggregates on ER calcium entry. We assessed the association of extracellular aggregated-α-synuclein (WT and A30P/A53T double-mutant) with the astrocytic membrane (lipid rafts) and studied its effects on membrane fluidity, ER stress, and ER calcium refilling in three systems-purified rat primary midbrain astrocyte culture, human iPSC-derived astrocytes, and U87 cells. The corresponding timeline effect on mitochondrial membrane potential was also evaluated. Post-24 h exposure to extracellular WT and mutant α-synuclein aggregates, fluorescence-based studies showed a significant increase in astrocyte membrane rigidity over control, with membrane association being significantly higher for the double mutant aggregates. α-Synuclein aggregates also showed preferentially higher association with lipid rafts of astrocytic membrane. A simultaneous increase in ER stress markers (phosphorylated PERK and CHOP) with significantly higher SOCE was also observed in aggregate-treated astrocytes, with higher levels for double mutant variant. These observations correlate with increased expression of SOCE markers, especially Orai3, on plasma membrane. Alterations in mitochondrial membrane potential were only noted post-48 h of exposure to α-synuclein aggregates. We therefore suggest that in astrocytes, α-synuclein-aggregates preferentially associate with lipid rafts of membrane, altering membrane fluidity and consequently inducing ER stress mediated by interaction with membrane SOCE proteins, resulting in higher Ca

Indexed as

alpha-SynucleinCalciumAnimalsAstrocytesCalcium SignalingEndoplasmic ReticulumHumansMembrane ProteinsRatsalpha-SynucleinCalciumMembrane ProteinsAstrocytesER stressExtracellular α-synucleinLipid raftMembrane associationMembrane fluidityMitochondrial membrane potentialSOCE

Identifiers

PMID37289385
OpenAlexW4379768724

What OpenQuestion holds

Textmetadata
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.