Evidence map›Paper›PMID 35527562›Full record

ArticleJournal of Parkinson's disease2022

The proSAAS Chaperone Provides Neuroprotection and Attenuates Transsynaptic α-Synuclein Spread in Rodent Models of Parkinson's Disease.

Iris Lindberg, Zhan Shu, Hoa Lam, Michael Helwig, Nur Yucer, Alexander Laperle, Clive N Svendsen, Donato A Di Monte, Nigel T Maidment

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
1.7field-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

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Iris LindbergUniversity of Maryland-Baltimore, Baltimore, MD, USA.
Zhan ShuUniversity of California at Los Angeles, Los Angeles, CA, USA.
Hoa LamUniversity of California at Los Angeles, Los Angeles, CA, USA.
Michael HelwigGerman Center for Neurodegenerative Disease (DZNE), Bonn, Germany.
Nur YucerBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Alexander LaperleBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Clive N SvendsenBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Donato A Di MonteGerman Center for Neurodegenerative Disease (DZNE), Bonn, Germany.
Nigel T MaidmentUniversity of California at Los Angeles, Los Angeles, CA, USA.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USGerman Center for Neurodegenerative Diseases · DEUniversity of Baltimore · US

Funding

ProSAAS-mediated neuroprotective mechanisms in Alzheimer's and Parkinson's diseases: the role of secretory chaperones in neurodegenerationR01AG062222 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI LINDBERG, IRIS, MAIDMENT, NIGEL T · 2019 to 2023
$3.5M
NIA NIH HHS R01 AG062222
6 · The paper itself

Abstract

backgroundParkinson's disease involves aberrant aggregation of the synaptic protein alpha-synuclein (aSyn) in the nigrostriatal tract. We have previously shown that proSAAS, a small neuronal chaperone, blocks aSyn-induced dopaminergic cytotoxicity in primary nigral cultures.

objectiveTo determine if proSAAS overexpression is neuroprotective in animal models of Parkinson's disease.

methodsproSAAS- or GFP-encoding lentivirus was injected together with human aSyn-expressing AAV unilaterally into the substantia nigra of rats and motor asymmetry assessed using a battery of motor performance tests. Dopamine neuron survival was assessed by nigral stereology and striatal tyrosine hydroxylase (TH) densitometry. To examine transsynaptic spread of aSyn, aSyn AAV was injected into the vagus of mice in the presence of AAVs encoding either GFP or proSAAS; the spread of aSyn-positive neurites into rostral nuclei was quantified following immunohistochemistry.

resultsCoinjection of proSAAS-encoding lentivirus profoundly reduced the motor asymmetry caused by unilateral nigral AAV-mediated human aSyn overexpression. This was accompanied by significant amelioration of the human aSyn-induced loss of both nigral TH-positive cells and striatal TH-positive terminals, demonstrating clear proSAAS-mediated protection of the nigrostriatal tract. ProSAAS overexpression reduced human aSyn protein levels in nigra and striatum and reduced the loss of TH protein in both regions. Following vagal administration of human aSyn-encoding AAV, the number of human aSyn-positive neurites in the pons and caudal midbrain was considerably reduced in mice coinjected with proSAAS-, but not GFP-encoding AAV, supporting proSAAS-mediated blockade of transsynaptic aSyn transmission.

conclusionThe proSAAS chaperone may represent a promising target for therapeutic development in Parkinson's disease.

Indexed as

alpha-SynucleinParkinson DiseaseAnimalsDisease Models, AnimalDopamineDopaminergic NeuronsMiceNeuroprotectionRatsRodentiaSubstantia NigraTyrosine 3-Monooxygenasealpha-SynucleinDopamineTyrosine 3-MonooxygenaseAlpha synucleinchaperonecytoprotectiondopamineParkinson’s diseasePCSK1NproSAAS

Identifiers

PMID35527562
PMCPMC9731515
OpenAlexW4229027844

What OpenQuestion holds

Textmetadata
LicenceTDM
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.