Evidence map›Paper›PMID 39929585›Full record

ReviewAdvances in pharmacology (San Diego, Calif.)2025

Neutral sphingomyelinase 2: A promising drug target for CNS disease.

Meixiang Huang, Matthew Stremlau, Jason Zavras, Cristina Zivko, Ajit G Thomas, Peter Pietri, Vasiliki Machairaki, Barbara S Slusher

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Advances in pharmacology (San Diego, Calif.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. 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

8 authors.

Meixiang HuangJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
Matthew StremlauJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
Jason ZavrasJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States.
Cristina ZivkoDepartment of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States; The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University School of Medicine, Baltimore, United States.
Ajit G ThomasJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
Peter PietriJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
Vasiliki MachairakiDepartment of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States; The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University School of Medicine, Baltimore, United States.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States. Electronic address: bslusher@jhmi.edu.

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
Development of neutral sphingomyelinase 2 (nSMase2) inhibitors for the treatment of Alzheimer's diseaseR01AG084728 · NIA · JOHNS HOPKINS UNIVERSITY · PI Rana Rais, Barbara Stauch Slusher · 2023 to 2026
$2.8M
Dendrimer-conjugated nSMase2 inhibitor as a novel therapeutic approach for Alzheimer's DiseaseR01AG063831 · NIA · JOHNS HOPKINS UNIVERSITY · PI RAIS, RANA, RANGARAMANUJAM, KANNAN · 2020 to 2024
$2.3M
NIA NIH HHS R01 AG063831NIA NIH HHS R01 AG084728NIMH NIH HHS P30 MH075673
6 · The paper itself

Abstract

Neutral sphingomyelinase 2 (nSMase2), encoded by the SMPD3 gene, is a pivotal enzyme in sphingolipid metabolism, hydrolyzing sphingomyelin to produce ceramide, a bioactive lipid involved in apoptosis, inflammation, membrane structure, and extracellular vesicle (EV) biogenesis. nSMase2 is abundantly expressed in the central nervous system (CNS), particularly in neurons, and its dysregulation is implicated in pathologies such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), prion diseases, and neuroviral diseases. In this review, we discuss the critical role of nSMase2 in the CNS and its involvement in neurological as well as non-neurological diseases. We explore the enzyme's functions in sphingolipid metabolism, its regulatory mechanisms, and the implications of its dysregulation in disease pathogenesis. The chapter highlights the therapeutic potential of pharmacologically targeting nSMase2 with small molecule inhibitors and emphasizes the need for further research to optimize inhibitor specificity and efficacy for clinical applications. By understanding the multifaceted roles of nSMase2, we aim to provide insights into novel therapeutic strategies for treating complex diseases associated with its dysregulation.

Indexed as

Central Nervous System DiseasesEnzyme InhibitorsSphingomyelin PhosphodiesteraseAnimalsHumansEnzyme InhibitorsSMPD3 protein, humanSphingomyelin PhosphodiesteraseAlzheimer’s disease (AD)Amyotrophic lateral sclerosis (ALS)Central nervous systemCeramideExtracellular vesicles (EVs)Neuroviral infectionsnSMase2Parkinson’s disease (PD)Prion diseasesSMPD3Sphingomyelin

Identifiers

PMID39929585
PMCPMC12172027

What OpenQuestion holds

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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.