Targeting d-Amino Acid Oxidase (DAAO) for the Treatment of Schizophrenia: Rationale and Current Status of Research

Kuo, Chien-Yi; Lin, Chieh‐Hsin; Lane, Hsien‐Yuan

doi:10.1007/s40263-022-00959-5

Cited by 7 publications

(5 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Low levels of the NMDA receptor co-agonist d -serine were found in the cerebrospinal fluid and post-mortem brains of schizophrenic patients, suggesting a possible functional contribution to NMDA receptor hypofunction. Moreover, schizophrenic patients were shown to have higher levels of d -amino acid oxidase, the peroxisomal flavoenzyme responsible for the metabolism of d- serine [ 130 , 131 ]. Early clinical trials employing d -serine as a supplementary treatment to antipsychotics showed significant improvements in positive, negative, and cognitive symptoms in schizophrenic patients.…”

Section: Glutamatergic Alterations In Schizophreniamentioning

confidence: 99%

See 1 more Smart Citation

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Nicosia,

Giovenzana,

Misztak

et al. 2024

IJMS

View full text Add to dashboard Cite

Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.

show abstract

Section: Glutamatergic Alterations In Schizophreniamentioning

confidence: 99%

“…Yet, these results have not been replicated in larger studies. Moreover, preclinical studies have shown that the potential antioxidant properties of d -amino acid oxidase inhibitors might be dependent on the dosage because high doses are associated with increased oxidative stress [ 131 , 135 , 136 ].…”

Section: Glutamatergic Alterations In Schizophreniamentioning

confidence: 99%

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Nicosia,

Giovenzana,

Misztak

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…D-amino acid oxidase (DAAO) plays a role in the pathogenesis of SCZ. It helps the metabolism of D-serine, the co-agonist at NMDAR [ 39 ]. NMDR hypofunction is found in SCZ, with decreased D-serine levels in peripheral blood and CSF [ 39 ].…”

Section: Novel Treatment Options For Schizophreniamentioning

confidence: 99%

“…It helps the metabolism of D-serine, the co-agonist at NMDAR [ 39 ]. NMDR hypofunction is found in SCZ, with decreased D-serine levels in peripheral blood and CSF [ 39 ]. SCZ is also associated with increased levels of DAAO in the brain.…”

Section: Novel Treatment Options For Schizophreniamentioning

confidence: 99%

“…Therefore, inhibiting DAAO activity results in increased levels of D-serine, enhancing the NMDAR function. DAAO antagonists, including sodium benzoate and luvadaxistat TAK-831, are promising novel compounds for treating SCZ [ 39 ]. BIIB-104 is an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-positive allosteric modulator that affects synaptic plasticity [ 6 ].…”

Section: Novel Treatment Options For Schizophreniamentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances in Psychopharmacology: From Bench to Bedside Novel Trends in Schizophrenia

Shah

Iqbal

2023

JPM

View full text Add to dashboard Cite

Research in the field of psychopharmacology is ongoing to develop novel compounds which can revolutionize the treatment of psychiatric disorders. The concept of bench-to-bedside is a tedious process, transforming the initial research performed in the laboratories into novel treatment options. Schizophrenia (SCZ) is a chronic psychiatric illness with significant morbidity and mortality. SCZ not only presents with psychotic symptoms including hallucinations and delusions but also with negative and cognitive symptoms. The negative symptoms include the diminished ability to express emotions, loss of pleasure, and motivation with minimal social interactions. Conventional antipsychotics primarily target positive symptoms with minimal therapeutic benefits for negative and cognitive symptoms along with metabolic side effects. Researchers have explored novel targets to develop new compounds to overcome the above limitations. The glutamatergic system has provided new hope in treating schizophrenia by targeting negative and cognitive symptoms. Other receptor modulators, including serotonergic, phosphodiesterase, trans-amine-associated receptors, etc., are novel targets for developing new compounds. Future research is required in this field to explore novel compounds and establish their efficacy and safety for the treatment of schizophrenia. Last but not least, pharmacogenomics has effectively utilized genetic information to develop novel compounds by minimizing the risk of failure of the clinical trials and enhancing efficacy and safety.

show abstract

Advances and challenges in serine in the central nervous system: physicochemistry, physiology, and pharmacology

Li,

Bai,

Zhang

2024

Metab Brain Dis

View full text Add to dashboard Cite

Targeting d-Amino Acid Oxidase (DAAO) for the Treatment of Schizophrenia: Rationale and Current Status of Research

Cited by 7 publications

References 117 publications

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Recent Advances in Psychopharmacology: From Bench to Bedside Novel Trends in Schizophrenia

Advances and challenges in serine in the central nervous system: physicochemistry, physiology, and pharmacology

Contact Info

Product

Resources

About