The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis
Open accessAbstract
We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the hippocampal dentate gyrus. We have further found that chemicals having efficacy in this in vivo screening assay also protect dopaminergic neurons of the substantia nigra following exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a mouse model of Parkinson disease. Here, we provide evidence that an active analog of P7C3, known as P7C3A20, protects ventral horn spinal cord motor neurons from cell death in the G93A-SOD1 mutant mouse model of amyotrophic lateral sclerosis (ALS). P7C3A20 is efficacious in this model when administered at disease onset, and protection from cell death correlates with preservation of motor function in assays of walking gait and in the accelerating rotarod test. The prototypical member of this series, P7C3, delays disease progression in G93A-SOD1 mice when administration is initiated substantially earlier than the expected time of symptom onset. Dimebon, an antihistaminergic drug with significantly weaker proneurogenic and neuroprotective efficacy than P7C3, confers no protection in this ALS model. We propose that the chemical scaffold represented by P7C3 and P7C3A20 may provide a basis for the discovery and optimization of pharmacologic agents for the treatment of ALS.
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“P7C3 was shown to be neuroprotective in mouse models of Parkinson disease137, Alzheimer disease157 and ALS158.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [158]
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Metadata
- Authors
- Tesla, R., Wolf, H. P., Xu, P., Drawbridge, J., Estill, S. J., Huntington, P., McDaniel, L., Knobbe, W., Burket, A., Tran, S., Starwalt, R., Morlock, L., Naidoo, J., Williams, N. S., Ready, J. M., McKnight, S. L., & Pieper, A. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Departments of bPsychiatry and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-10
- Volume
- 109
- Issue
- 42
- Pages
- 17016-17021
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3479516
- OpenAlex
- W2158315174
- Cited by
- 129
- References
- 31
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 8 · 2020: 12 · 2019: 8 · 2018: 15 · 2017: 15 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 7 · 2012: 2
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ca095471-10)
- National Institute of Mental Health (R01MH087986)
- National Cancer Institute (P01-CA095471)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Keywords
- amyotrophic lateral sclerosis, neuroprotection, SOD1 G93A mice, motor neuron survival, spinal motoneurons, disease-modifying therapy, early treatment initiation, dimebon, Parkinson's disease, MPTP, dopaminergic neurons, substantia nigra
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Carbazoles, Indoles, Motor Activity, Motor Neurons, Spinal Cord, Polymerase Chain Reaction, Neuroprotective Agents, Rotarod Performance Test, Mice
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