Evidence map›Paper›PMID 42845352›Full record

ArticlebioRxiv : the preprint server for biology2026

A guanosine metabolism-bioenergetics intersection drives Parkinson's disease.

Alexandros C Kokotos, Santiago R Unda, Paula Reyes-Pérez, Mariam Isayan, Maria Teresa Periñan, Michael G Kaplitt, Timothy A Ryan

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Alexandros C KokotosDepartment of Biochemistry & Biophysics, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-4024-9866
Santiago R UndaDepartment of Neurosurgery, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0001-7319-6794
Paula Reyes-PérezLaboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Autónoma de México, Querétaro, México.ORCID 0000-0001-8062-7441
Mariam IsayanGenomic Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, United States of America.ORCID 0009-0002-2387-5347
Maria Teresa PeriñanCentre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; Unidad de Trastornos del Movimiento, Servicio de Neurología, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.ORCID 0000-0001-7412-7440
Michael G KaplittDepartment of Neurosurgery, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0002-8979-2459
Timothy A RyanDepartment of Biochemistry & Biophysics, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0003-2533-9548

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several Parkinson's Disease (PD) linked mutations are known to drive deficits in a pathway that relies on an adequate supply of guanosine nucleotide triphosphate (GTP) to drive cellular neuronal processes. Similarly, there is strong evidence that a deficit in bioenergetic support for neuron function is also a major genetic driver of PD. We show here that the reliance on these two purine-based metabolites intersect at another PD susceptibility gene that encodes nucleoside diphosphate kinase (NDK) which converts ATP into GTP. We show that overexpression of NDK is strongly protective both in-vivo and in-vitro to metabolic lesions and identify mutations in NDK in humans associated both with increased risk and protection from PD. We discovered that NDK lies at the intersection of proper ATP production, de novo synthesis of guanosine diphosphate and the activity of GTP cyclohydrolase I, a consumptive pathway needed to produce the bioactive metabolite tetrahydrobiopterin (BH

Identifiers

PMID42845352
PMCPMC13640495

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.