Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various factors are thought to be involved in the pathogenesis of schizophrenia. Recently, biochemical studies using human samples and animal models suggest that oxidative stress and the resulting formation of reactive carbonyl compounds (RCOs) contribute to the pathophysiology of schizophrenia. The accumulation of RCOs, carbonyl stress, results in the modification of proteins and formation of advanced glycation end products (AGEs), such as pentosidine. We previously reported that a certain subtype of schizophrenic patients exhibit idiopathic carbonyl stress with high plasma pentosidine levels and the depletion of vitamin B6, without underlying diabetes or chronic kidney disease, the two major causes of elevated AGEs. Agents able to inhibit AGE formation or entrap carbonyl compounds may also prove to be of therapeutic value. Pyridoxamine, a non-toxic, water-soluble vitamin B6, has potent abilities to entrap toxic carbonyl compounds and prevent toxicity. In particular, the markedly lowered vitamin B6 levels in schizophrenic patients with high pentosidine levels suggest that pyridoxamine may prove to be clinically useful.
 ...
PMID:[Carbonyl stress-related schizophrenia--perspective on future therapy and hypotheses regarding pathophysiology of schizophrenia]. 2256 54

Glyoxalase I (GLO1) is an enzyme essential for the cellular detoxification of reactive carbonyl compounds. Its impairment leads to carbonyl stress and the eventual formation of advanced glycation end products (AGEs) including pentosidine. In the present study, we provide for the first time evidence of genetic abnormalities in GLO1 with their attendant derangements of biochemistry in a small population of schizophrenia. We found that seventeen schizophrenia (approximately 17.4%) showed increases in plasma pentosidine content although they have no physical complications, and concomitantly marked decrease of pyridoxal levels was found in schizophrenia. Vitamin B6 exists in three forms, i.e., pyridoxine, pyridoxal and pyridoxamine. Pyridoxamine has potent ability to entrap RCOs and prevent their toxicity. Further study of profiling of metabolomics and clinical manifestations in schizophrenia could pave the way for novel, better therapeutic/preventive measures for this devastating disease.
 ...
PMID:[Schizophrenia and carbonyl stress]. 2256 12

Accumulating evidence suggests that advanced glycation end products, generated as a consequence of facilitated carbonyl stress, are implicated in the development of a variety of diseases. These diseases include neurodegenerative illnesses, such as Alzheimer disease. Pyridoxamine is one of the 3 forms of vitamin B6, and it acts by combating carbonyl stress and inhibiting the formation of AGEs. Depletion of pyridoxamine due to enhanced carbonyl stress eventually leads to a decrease in the other forms of vitamin B6, namely pyridoxal and pyridoxine. We previously reported that higher levels of plasma pentosidine, a well-known biomarker for advanced glycation end products, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. However, there is as yet no clinical characterization of this subset of schizophrenia. In this study, we found that these patients shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, low educational status, longer durations of hospitalization, and higher doses of antipsychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients.
...
PMID:Clinical features of schizophrenia with enhanced carbonyl stress. 2406 94

We have identified idiopathic carbonyl stress in a subpopulation of schizophrenic patients. We first identified a patient with a mutation in GLO1 (glyoxalase I) who showed increased AGE (advanced glycation end-product) levels and decreased vitamin B6 levels. By applying the observations from this rare case to the general schizophrenic population, we were able to identify a subset of patients (20%) for whom carbonyl stress may represent a causative pathophysiological process. Genetic defects in GLO1 increase the risk of carbonyl stress 5-fold, and the resulting increased AGE levels correlate significantly with PANSS (Positive and Negative Syndrome Scale) scored negative symptoms. Pyridoxamine, an active form of vitamin B6 and scavenger for carbonyl stress, could represent a novel and efficacious therapeutic agent for these treatment-resistant symptoms. In the present article, we describe a unique research approach to identify the causative process in the pathophysiology of a subset of schizophrenia. Our findings could form the basis of a schizophrenia subtype classification within this very heterogeneous disease and ultimately lead to better targeted therapy.
...
PMID:Carbonyl stress in schizophrenia. 2464 62