ArticleJournal of pineal research2023
Biosynthesis of neuroprotective melatonin is dysregulated in Huntington's disease.
Article in Journal of pineal research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Dysregulation of melatonin rhythm in Parkinson's and Huntington's disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2025Pooled it
- Harnessing spatiotemporal melatonin delivery from engineered platforms for targeted microenvironment remodeling in peripheral neuropathy.Materials today. Bio · 2026Review
- Tryptophan metabolism alterations in neurological and psychiatric diseases: Molecular mechanisms and pharmacological targets.Metabolic brain disease · 2026Review
- Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases.Biology · 2026Review
- Regulation of nuclear transport of the transcriptional factor REST improves axon regeneration in peripheral nerves.Molecular medicine reports · 2025Article
- Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.Journal of neuroendocrinology · 2025Review
- The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology.Antioxidants (Basel, Switzerland) · 2025Review
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Melatonin Deficits Result in Pathologic Metabolic Reprogramming in Differentiated Neurons.Journal of pineal research · 2025Article
- Intrinsically synthesized melatonin in mitochondria and factors controlling its production.Histology and histopathology · 2025Review
- Exploring the association between melatonin and nicotine dependence (Review).International journal of molecular medicine · 2024Review
- Circadian Interventions in Preclinical Models of Huntington's Disease: A Narrative Review.Biomedicines · 2024Review
- Melatonin in animal husbandry: functions and applications.Frontiers in veterinary science · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, AANAT mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.
Indexed as
Identifiers
What OpenQuestion holds
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.