ArticlePLoS biology2016
NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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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.
The trial behind it
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Who cites it
89 citing papers in PubMed, 130 citations in OpenAlex.
- Redox Molecules in Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2026Review
- Neurodegenerative NMNAT2 Deficiency Promotes APP Processing in a SARM1-Dependent Manner.Cells · 2026Article
- The Pof1 nicotinamide mononucleotide adenylyl transferase has a non-canonical role in NADThe Journal of biological chemistry · 2026Article
- Potent Neuronal Nicotinamide Adenine Dinucleotide-Boosting Tetrahydroquinoxalines: Structure-Activity Relationships and Early Drug Metabolism and Pharmacokinetics Evaluation.ACS medicinal chemistry letters · 2026Article
- Transcriptional regulation of human NMNAT2: insights from 3D genome sequencing and bioinformatics.The FEBS journal · 2026Article
- Article
- The nicotinamide mononucleotide adenylyl transferase (NMNAT/Nma1) modulates phosphate-sensing (PHO) signaling independent of its NAD+ synthesis activity in Saccharomyces cerevisiae.FEMS yeast research · 2026Article
- NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial NMNAT3 reduces amyloid aggregates inMitochondrial communications · 2026Article
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- Chronically Low NMNAT2 Expression Causes Sub-lethal SARM1 Activation and Altered Response to Nicotinamide Riboside in Axons.Molecular neurobiology · 2025Article
- Programmed neurite degeneration in human central nervous system neurons driven by changes in NADCell death & disease · 2025Article
- NMNAT2 is a druggable target to drive neuronal NAD production.Nature communications · 2024Article
- Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications.Metabolites · 2024Review
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.Molecular neurodegeneration · 2024Article
- The Role of NMNAT2/SARM1 in Neuropathy Development.Biology · 2024Review
- Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.Molecular neurodegeneration · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is neuroprotective in numerous preclinical models of neurodegeneration. Here, we show that brain nmnat2 mRNA levels correlate positively with global cognitive function and negatively with AD pathology. In AD brains, NMNAT2 mRNA and protein levels are reduced. NMNAT2 shifts its solubility and colocalizes with aggregated Tau in AD brains, similar to chaperones, which aid in the clearance or refolding of misfolded proteins. Investigating the mechanism of this observation, we discover a novel chaperone function of NMNAT2, independent from its enzymatic activity. NMNAT2 complexes with heat shock protein 90 (HSP90) to refold aggregated protein substrates. NMNAT2's refoldase activity requires a unique C-terminal ATP site, activated in the presence of HSP90. Furthermore, deleting NMNAT2 function increases the vulnerability of cortical neurons to proteotoxic stress and excitotoxicity. Interestingly, NMNAT2 acts as a chaperone to reduce proteotoxic stress, while its enzymatic activity protects neurons from excitotoxicity. Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health.
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Registered trials
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.