Evidence mapPaperPMID 42154377Full record

ReviewMetabolic brain disease2026

Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.

Janvi Verma, Rohit Kumar Singh, Supratim Paul, Sumedha Gupta, Abhishek Kumar Gupta, Arun Kumar Sharma, Manjeet Kumar, Sidharth Mehan, Rajaram Samant, Manoj Tongra

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In one paragraph

Review in Metabolic brain disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

10 authors.

Janvi VermaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Rohit Kumar SinghDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Supratim PaulDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Sumedha GuptaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Abhishek Kumar GuptaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Arun Kumar SharmaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Manjeet KumarDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Sidharth MehanDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India. sidharthmehan@isfcp.org.ORCID http://orcid.org/0000-0003-0034-835X
Rajaram SamantChief Scientific Officer, Celagenex Research, Thane, Mumbai, India.
Manoj TongraChief Scientific Officer, Celagenex Research, Thane, Mumbai, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Although traditionally linked to synaptic protein dysfunction and neurotransmitter imbalance, growing evidence suggests that broader intracellular signaling networks critically regulate the neurodevelopmental processes disrupted in ASD. This review synthesizes current evidence on four interconnected signaling pathways-Klotho, GDNF/GFRA-1, IGF-1, and GLP-1-and examines their potential roles in ASD pathophysiology within a unified mechanistic framework. These pathways regulate fundamental processes, including neuronal survival, synaptogenesis, dendritic maturation, myelination, modulation of oxidative stress, neuroinflammation, and metabolic homeostasis. Importantly, they converge on shared intracellular cascades such as PI3K/Akt, MAPK/ERK, mTOR, and Wnt/β-catenin, which are increasingly implicated in ASD-related abnormalities in synaptic plasticity and circuit organization. Experimental models demonstrate that dysregulation of these signaling systems can impair hippocampal function, alter excitatory-inhibitory balance, and disrupt structural connectivity. Among them, IGF-1 has shown promising translational potential in clinical trials for syndromic ASD, while GLP-1 receptor agonists and Klotho modulation represent emerging therapeutic avenues. The GDNF/GFRA-1 axis further highlights the importance of trophic support in maintaining synaptic integrity and neuronal resilience. By integrating molecular, preclinical, and clinical findings, this review proposes that convergent dysregulation of trophic and metabolic signaling pathways may contribute to ASD heterogeneity. A systems-level understanding of these interconnected mechanisms may facilitate biomarker development and support the advancement of stratified, pathway-targeted therapeutic strategies.

Indexed as

Autism Spectrum DisorderGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor ReceptorsGlucagon-Like Peptide 1Insulin-Like Growth Factor IKlotho ProteinsSignal TransductionAnimalsHumansGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor ReceptorsGlucagon-Like Peptide 1Insulin-Like Growth Factor IKlotho ProteinsKL protein, humanAutism spectrum disorderGDNF/GFRA-1 pathwayGLP-1 receptorIGF-1 signalingKlotho signalingPI3K/Akt/mTOR pathway

Identifiers

What Socratic holds

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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 Socratic graph.