ALDH4A1 expression levels are elevated in postmortem brains of patients with schizophrenia and are associated with genetic variants in enzymes related to proline metabolism

Nagaoka, Atsuko; Kunii, Yasuto; Hino, Mizuki; Izumi, Ryuta; Nagashima, Chisato; Takeshima, Akari; Sainouchi, Makoto; Nawa, Hiroyuki; Kakita, Akiyoshi

doi:10.1016/j.jpsychires.2020.02.001

Cited by 10 publications

(14 citation statements)

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“… 81 In addition, patients with ALDH4A1 gene deficiency suffer from schizoaffective disorders and schizophrenia, and the potential molecular mechanism is also associated with abnormal proline metabolism. 82 A recent study discovers that circulating ALDH4A1 is significantly elevated in the plasma of mice and humans with atherosclerosis, and the administration of ALDH4A1 antibody can protect against atherosclerosis progression. These results support that ALDH4A1 can be used as a putative disease biomarker and therapeutic target.…”

Section: Aldhs As Diagnosis Markers In Non‐tumor Diseasesmentioning

confidence: 99%

“…Associated proteins of ALDH4A1 can potentially be used as pharmacological chaperones to stabilize the misfolded variants of ALDH4A1 in patients with HPII 81 . In addition, patients with ALDH4A1 gene deficiency suffer from schizoaffective disorders and schizophrenia, and the potential molecular mechanism is also associated with abnormal proline metabolism 82 . A recent study discovers that circulating ALDH4A1 is significantly elevated in the plasma of mice and humans with atherosclerosis, and the administration of ALDH4A1 antibody can protect against atherosclerosis progression.…”

Section: Aldhs As Diagnosis Markers In Non‐tumor Diseasesmentioning

confidence: 99%

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Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Xia

Liu

et al. 2023

MedComm

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The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation of endogenous and exogenous aldehydes to carboxylic acids, which contributes to cellular and tissue homeostasis. ALDHs play essential parts in detoxification, biosynthesis, and antioxidants, which are of important value for cell proliferation, differentiation, and survival in normal body tissues. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Notably, the involvement of the ALDHs in tumor progression is responsible for the maintenance of the stem‐cell‐like phenotype, triggering rapid and aggressive clinical progressions. ALDHs have captured increasing attention as biomarkers for disease diagnosis and prognosis. Nevertheless, these require further longitudinal clinical studies in large populations for broad application. This review summarizes our current knowledge regarding ALDHs as potential biomarkers in tumors and several non‐tumor diseases, as well as recent advances in our understanding of the functions and underlying molecular mechanisms of ALDHs in disease development. Finally, we discuss the therapeutic potential of ALDHs in diseases, especially in tumor therapy with an emphasis on their clinical implications.

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Section: Aldhs As Diagnosis Markers In Non‐tumor Diseasesmentioning

confidence: 99%

Section: Aldhs As Diagnosis Markers In Non‐tumor Diseasesmentioning

confidence: 99%

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Xia

Liu

et al. 2023

MedComm

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“…Human patients with genetic defects in PRODH (HPI, L-Pro levels up to 10-fold higher than normal) or in P5CDH (ALDH4A1; HPII, L-Pro levels up to 15-fold higher and P5C excretion) suffer schizoaffective disorders and schizophrenia (Table 2; Liu et al, 2002;Bender et al, 2005;Raux et al, 2007;Clelland et al, 2011;Nagaoka et al, 2020). At high levels, L-Pro can be oxidized/converted into the neurotransmitter Lglutamate, which is associated with schizophrenia (Figure 5).…”

Section: Schizophrenia Induction and Neurotoxicitymentioning

confidence: 99%

The Multifaceted Roles of Proline in Cell Behavior

Patriarca

Cermola

D’Aniello

et al. 2021

Front. Cell Dev. Biol.

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Herein, we review the multifaceted roles of proline in cell biology. This peculiar cyclic imino acid is: (i) A main precursor of extracellular collagens (the most abundant human proteins), antimicrobial peptides (involved in innate immunity), salivary proteins (astringency, teeth health) and cornifins (skin permeability); (ii) an energy source for pathogenic bacteria, protozoan parasites, and metastatic cancer cells, which engage in extracellular-protein degradation to invade their host; (iii) an antistress molecule (an osmolyte and chemical chaperone) helpful against various potential harms (UV radiation, drought/salinity, heavy metals, reactive oxygen species); (iv) a neural metabotoxin associated with schizophrenia; (v) a modulator of cell signaling pathways such as the amino acid stress response and extracellular signal-related kinase pathway; (vi) an epigenetic modifier able to promote DNA and histone hypermethylation; (vii) an inducer of proliferation of stem and tumor cells; and (viii) a modulator of cell morphology and migration/invasiveness. We highlight how proline metabolism impacts beneficial tissue regeneration, but also contributes to the progression of devastating pathologies such as fibrosis and metastatic cancer.

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“…Human postmortem brain analysis Brain lysates of the prefrontal cortex BA10 and the superior temporal gyrus BA22 were prepared with N-PER (#87792, Thermo Fisher) supplemented with a protease inhibitor cocktail (Calbiochem) and PhosSTOP phosphatase inhibitor cocktail (Roche) and then cleared by centrifugation at 40,000 3 g and 4 C for 30 min, as previously described (Nagaoka et al, 2020). The KIF3A and KIF3B protein levels were quantified by direct ELISA as previously described (Crowther, 2001).…”

Section: Materials Availabilitymentioning

confidence: 99%

Betaine ameliorates schizophrenic traits by functionally compensating for KIF3-based CRMP2 transport

et al. 2021

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ALDH4A1 expression levels are elevated in postmortem brains of patients with schizophrenia and are associated with genetic variants in enzymes related to proline metabolism

Cited by 10 publications

References 42 publications

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

The Multifaceted Roles of Proline in Cell Behavior

Betaine ameliorates schizophrenic traits by functionally compensating for KIF3-based CRMP2 transport

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