ArticleThe Journal of biological chemistry2011
Phenylbutyrate up-regulates the DJ-1 protein and protects neurons in cell culture and in animal models of Parkinson disease.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 89 papers, 2 of them syntheses that pooled it.
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
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.
Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
A Pharmacokinetic and Pharmacodynamic Study of AMX0035 in Patients With ALS
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson's Disease and Neuroprotective Effects-Therapeutic Approaches: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.The New England journal of medicine · 2020Trial
- 4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.Neurochemical research · 2026Article
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease.Biomolecules · 2025Review
- Epigenetic regulation of iron metabolism and ferroptosis in Parkinson's disease: Identifying novel epigenetic targets.Acta pharmacologica Sinica · 2025Review
- Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.Cellular and molecular neurobiology · 2025Review
- Chaperone-mediated autophagy manipulates PGC1α stability and governs energy metabolism under thermal stress.Nature communications · 2025Article
- Impact of ER stress and the unfolded protein response on Fabry disease.EBioMedicine · 2025Review
- Drug repurposing in amyotrophic lateral sclerosis (ALS).Expert opinion on drug discovery · 2025Review
- HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- The role of gut-derived short-chain fatty acids in Parkinson's disease.Neurogenetics · 2024Review
- Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue.Biomolecules · 2024Article
- Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.Epigenomics · 2024Review
- Article
- Trends and hotspots on the relationship between gut microbiota and Parkinson's Disease: a bibliometric analysis.Frontiers in cellular and infection microbiology · 2024Review
- Parkinson's disease and gut microbiota: from clinical to mechanistic and therapeutic studies.Translational neurodegeneration · 2023Review
- Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells.Cellular & molecular biology letters · 2023Article
- Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us.International journal of molecular sciences · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson disease is caused by the death of midbrain dopamine neurons from oxidative stress, abnormal protein aggregation, and genetic predisposition. In 2003, Bonifati et al. (23) found that a single amino acid mutation in the DJ-1 protein was associated with early-onset, autosomal recessive Parkinson disease (PARK7). The mutation L166P prevents dimerization that is essential for the antioxidant and gene regulatory activity of the DJ-1 protein. Because low levels of DJ-1 cause Parkinson, we reasoned that overexpression might stop the disease. We found that overexpression of DJ-1 improved tolerance to oxidative stress by selectively up-regulating the rate-limiting step in glutathione synthesis. When we imposed a different metabolic insult, A53T mutant α-synuclein, we found that DJ-1 turned on production of the chaperone protein Hsp-70 without affecting glutathione synthesis. After screening a number of small molecules, we have found that the histone deacetylase inhibitor phenylbutyrate increases DJ-1 expression by 300% in the N27 dopamine cell line and rescues cells from oxidative stress and mutant α-synuclein toxicity. In mice, phenylbutyrate treatment leads to a 260% increase in brain DJ-1 levels and protects dopamine neurons against 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) toxicity. In a transgenic mouse model of diffuse Lewy body disease, long-term administration of phenylbutyrate reduces α-synuclein aggregation in brain and prevents age-related deterioration in motor and cognitive function. We conclude that drugs that up-regulate DJ-1 gene expression may slow the progression of Parkinson disease by moderating oxidative stress and protein aggregation.
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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.