ArticleBrain : a journal of neurology2015
Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment.
Article in Brain : a journal of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 77 citations in OpenAlex.
- SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis.International journal of molecular sciences · 2024Article
- Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice.Current issues in molecular biology · 2024Article
- Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation.Lipids in health and disease · 2023Article
- NADProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Balancing NADCellular and molecular life sciences : CMLS · 2022Review
- The Legend of ATP: From Origin of Life to Precision Medicine.Metabolites · 2022Review
- Role of mitophagy in the neurodegenerative diseases and its pharmacological advances: A review.Frontiers in molecular neuroscience · 2022Review
- Mitophagy: An Emergence of New Player in Alzheimer's Disease.Frontiers in molecular neuroscience · 2022Review
- Efficient Assay and Marker Significance of NADFrontiers in medicine · 2022Article
- A New Insight into an Alternative Therapeutic Approach to Restore Redox Homeostasis and Functional Mitochondria in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2021Review
- Aberrant NADNature metabolism · 2021Article
- NADEMBO molecular medicine · 2021Review
- Nicotinamide Riboside and Pterostilbene Cooperatively Delay Motor Neuron Failure in ALS SOD1Molecular neurobiology · 2021Article
- Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2020Review
- Interplay between NADBiochimica et biophysica acta. Molecular basis of disease · 2019Review
- Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer's disease pathogenesis.Neuroscience letters · 2019Review
- Phenothiazine normalizes the NADH/NADRedox biology · 2019Article
- GRP75 overexpression rescues frataxin deficiency and mitochondrial phenotypes in Friedreich ataxia cellular models.Human molecular genetics · 2019Article
- A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD.Frontiers in aging neuroscience · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD(+)) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD(+) followed by decreased ATP production, and are completely rescued by treatment with NAD(+) or its precursor nicotinamide because of restoration of physiological NAD(+) levels. Toxic prion protein-induced NAD(+) depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD(+). Intranasal NAD(+) treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD(+) starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD(+) replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases.
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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.