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Record W2766855729 · doi:10.3233/jpd-171240

Is the Enzyme ACMSD a Novel Therapeutic Target in Parkinson’s Disease?

2017· review· en· W2766855729 on OpenAlexfundno aff
Keerthi Thirtamara Rajamani, Peipei Li, Martha L. Escobar Galvis, Viviane Labrie, Patrik Brundin, Lena Brundin

Bibliographic record

VenueJournal of Parkinson s Disease · 2017
Typereview
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsnot available
FundersNational Institute on Deafness and Other Communication DisordersNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthNational Institutes of HealthAlzheimer's SocietyBrain and Behavior Research FoundationMichael J. Fox Foundation for Parkinson's ResearchScottish Rite Charitable Foundation of CanadaU.S. Department of Defense
KeywordsQuinolinic acidParkinson's diseaseBiologyKynurenine pathwayNeurotoxinGeneticsPathogenesisEnzymeSomatic hypermutationGeneCell biologyBiochemistryDiseaseKynurenineTryptophanImmunologyMedicineAmino acidInternal medicine

Abstract

fetched live from OpenAlex

Several large genome wide association studies have identified a locus in close proximity to the gene encoding the enzyme aminocarboxymuconate-semialdehyde-decarboxylase (ACMSD) to be associated with the risk for Parkinson's disease (PD), tentatively suggesting that this enzyme might influence PD pathogenesis. Further support for this comes from the recent identification of a disease-segregating stop codon mutation in ACMSD in a family with Parkinsonism, and a missense mutation in the ACMSD gene predicted to disrupt enzyme function in an individual with typical PD. ACMSD is part of the kynurenine pathway, responsible for the catalytic breakdown of tryptophan into NAD+, generating several neuroactive metabolites in the process. The enzyme is located at a key branch-point of the pathway, limiting the production of the neurotoxin quinolinic acid, which has excitotoxic and inflammatory properties. In this review, we discuss the genetic findings in light of the functions of ACMSD and its potential involvement in PD pathogenesis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.965
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0030.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.139
GPT teacher head0.370
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations36
Published2017
Admission routes1
Has abstractyes

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