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Role of glyoxalase 1 in methylglyoxal detoxification-the broad player of psychiatric disorders.

ABSTRACT: Methylglyoxal (MG) is a highly reactive α-ketoaldehyde formed endogenously as a byproduct of the glycolytic pathway. To remove MG, various detoxification systems work together in vivo, including the glyoxalase system, which enzymatically degrades MG using glyoxalase 1 (GLO1) and GLO2. Recently, numerous reports have shown that GLO1 expression and MG accumulation in the brain are involved in the pathogenesis of psychiatric disorders, such as anxiety disorder, depression, autism, and schizophrenia. Furthermore, it has been reported that GLO1 inhibitors may be promising drugs for the treatment of psychiatric disorders. In this review, we discuss the recent findings of the effects of altered GLO1 function on mental behavior, especially focusing on results obtained from animal models.

SUBMITTER: Toriumi K

PROVIDER: S-EPMC8718652 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Role of glyoxalase 1 in methylglyoxal detoxification-the broad player of psychiatric disorders.

Toriumi Kazuya K Miyashita Mitsuhiro M Suzuki Kazuhiro K Tabata Koichi K Horiuchi Yasue Y Ishida Hiroaki H Itokawa Masanari M Arai Makoto M

Redox biology 20211222

Methylglyoxal (MG) is a highly reactive α-ketoaldehyde formed endogenously as a byproduct of the glycolytic pathway. To remove MG, various detoxification systems work together in vivo, including the glyoxalase system, which enzymatically degrades MG using glyoxalase 1 (GLO1) and GLO2. Recently, numerous reports have shown that GLO1 expression and MG accumulation in the brain are involved in the pathogenesis of psychiatric disorders, such as anxiety disorder, depression, autism, and schizophrenia ...[more]

PMID: 34953453

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Project description:Suicide is a leading cause of death worldwide. In 2020, some 12.2 million Americans seriously contemplated suicide, 3.2 million planned suicide attempts, and 1.2 million attempted suicide. Traditionally, the approach to treating suicidal behavior (SB) has been to treat the "underlying" psychiatric disorder. However, the number of diagnoses associated with SB is considerable. We could find no studies describing the range of disorders reported to be comorbid with SB. This narrative review summarizes literature documenting the occurrence of SB across the lifespan and the full range of psychiatric diagnoses, not only BPD and those that comprise MDE, It also describes the relevance of these observations to clinical practice, research, and nosology. The literature searches contained the terms "suicid*" and each individual psychiatric diagnosis and identified 587 studies. We did not include case reports, case series, studies only addressing suicidal ideation or non-suicidal self-injury (NSSI), studies on self-harm, not distinguishing between SB and NSSI and studies that did not include any individuals that met criteria for a specific DSM-5 diagnosis (n = 366). We found that SB (suicide and/or suicide attempt) was reported to be associated with 72 out of 145 diagnoses, although data quality varied. Thus, SB is not exclusively germane to Major Depressive Episode (MDE) and Borderline Personality Disorder (BPD), the only conditions for which it is a diagnostic criterion. That SB co-occurs with so many diagnoses reinforces the need to assess current and past SB regardless of diagnosis, and supports the addition of charting codes to the DSM-5 to indicate current or past SB. It also comports with new data that specific genes are associated with SB independent of psychiatric diagnoses, and suggests that SB should be managed with specific suicide prevention interventions in addition to treatments indicated for co-occurring diagnoses. SB diagnostic codes would help researchers and clinicians document and measure SB's trajectory and response to treatment over time, and, ultimately, help develop secondary and tertiary prevention strategies. As a separate diagnosis, SB would preclude situations in which a potentially life-threatening behavior is not accounted for by a diagnosis, a problem that is particularly salient when no mental disorder is present, as is sometimes the case.

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Role of glyoxalase 1 in methylglyoxal detoxification-the broad player of psychiatric disorders.

Publications

Role of glyoxalase 1 in methylglyoxal detoxification-the broad player of psychiatric disorders.

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