d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia

doi:10.3390/ijms222010917

Review

. 2021 Oct 9;22(20):10917.

doi: 10.3390/ijms222010917.

d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia

Yu-Jung Cheng^{1

2}, Chieh-Hsin Lin^{3

4

5

6}, Hsien-Yuan Lane^{3

4

7

8}

Affiliations

¹ Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 40402, Taiwan.
² Department of Rehabilitation, China Medical University Hospital, Taichung 40402, Taiwan.
³ Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan.
⁴ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
⁵ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
⁶ School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁷ Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan.
⁸ Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan.

PMID: 34681579
PMCID: PMC8535920
DOI: 10.3390/ijms222010917

Review

d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia

Yu-Jung Cheng et al. Int J Mol Sci. 2021.

. 2021 Oct 9;22(20):10917.

doi: 10.3390/ijms222010917.

Authors

Yu-Jung Cheng^{1

2}, Chieh-Hsin Lin^{3

4

5

6}, Hsien-Yuan Lane^{3

4

7

8}

Affiliations

¹ Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 40402, Taiwan.
² Department of Rehabilitation, China Medical University Hospital, Taichung 40402, Taiwan.
³ Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan.
⁴ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
⁵ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
⁶ School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁷ Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan.
⁸ Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan.

PMID: 34681579
PMCID: PMC8535920
DOI: 10.3390/ijms222010917

Abstract

Numerous studies over the last several years have shown that d-amino acids, especially d-serine, have been related to brain and neurological disorders. Acknowledged neurological functions of d-amino acids include neurotransmission and learning and memory functions through modulating N-methyl-d-aspartate type glutamate receptors (NMDARs). Aberrant d-amino acids level and polymorphisms of genes related to d-amino acids metabolism are associated with neurodegenerative brain conditions. This review summarizes the roles of d-amino acids and pLG72, also known as d-amino acid oxidase activator, on two neurodegenerative disorders, schizophrenia and Alzheimer's disease (AD). The scope includes the changes in d-amino acids levels, gene polymorphisms of G72 genomics, and the role of pLG72 on NMDARs and mitochondria in schizophrenia and AD. The clinical diagnostic value of d-amino acids and pLG72 and the therapeutic importance are also reviewed.

Keywords: Alzheimer’s disease; d-amino acids; pLG72; schizophrenia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Illustration of the serine shuttle model. d-serine is converted from l-serine by serine racemase (SR) in astrocytes and presynaptic neurons. In astrocytes, d-serine also accumulates in vesicles. d-serine can be shuttled from neurons to astrocytes by alanine-serine-cysteine-1 transporter (Asc-1) and alanine, serine, cysteine, and threonine exchangers (ASCT1), whereas l-serine is shuttled from astrocytes to neurons by the same transporters in the opposite direction. The excessive d-serine in the synaptic cleft is removed by Asc-1 (created with BioRender.com accessed on 25 September 2021).

**Figure 2**
The DAAO–pLG72 interaction in d-serine degradation and mitochondria stress. d-serine is degraded by DAAO in astrocytes. pLG72, when on the mitochondrial outer membrane, can bind and inhibit DAAO. Overexpressed pLG72 on mitochondria also induces mitochondria fragmentation and oxidative stress (created with BioRender.com accessed on 25 September 2021).

See this image and copyright information in PMC

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References

1. Gnegy M.E. Ca2+/calmodulin signaling in NMDA-induced synaptic plasticity. Crit. Rev. Neurobiol. 2000;14:91–129. doi: 10.1615/CritRevNeurobiol.v14.i2.10. - DOI - PubMed
1. Piubelli L., Murtas G., Rabattoni V., Pollegioni L. The Role of D-Amino Acids in Alzheimer’s Disease. J. Alzheimers Dis. 2021;80:475–492. doi: 10.3233/JAD-201217. - DOI - PubMed
1. Seckler J.M., Lewis S.J. Advances in D-Amino Acids in Neurological Research. Int. J. Mol. Sci. 2020;21:7325. doi: 10.3390/ijms21197325. - DOI - PMC - PubMed
1. Di Maria E., Bonvicini C., Bonomini C., Alberici A., Zanetti O., Gennarelli M. Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer’s disease. J. Alzheimers Dis. 2009;18:953–960. doi: 10.3233/JAD-2009-1194. - DOI - PubMed
1. Lin E., Lin C.H., Lai Y.L., Huang C.H., Huang Y.J., Lane H.Y. Combination of G72 Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches. Front. Psychiatry. 2018;9:566. doi: 10.3389/fpsyt.2018.00566. - DOI - PMC - PubMed

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[1] Gnegy M.E. Ca2+/calmodulin signaling in NMDA-induced synaptic plasticity. Crit. Rev. Neurobiol. 2000;14:91–129. doi: 10.1615/CritRevNeurobiol.v14.i2.10. - DOI - PubMed

[2] Gnegy M.E. Ca2+/calmodulin signaling in NMDA-induced synaptic plasticity. Crit. Rev. Neurobiol. 2000;14:91–129. doi: 10.1615/CritRevNeurobiol.v14.i2.10. - DOI - PubMed

[3] Piubelli L., Murtas G., Rabattoni V., Pollegioni L. The Role of D-Amino Acids in Alzheimer’s Disease. J. Alzheimers Dis. 2021;80:475–492. doi: 10.3233/JAD-201217. - DOI - PubMed

[4] Piubelli L., Murtas G., Rabattoni V., Pollegioni L. The Role of D-Amino Acids in Alzheimer’s Disease. J. Alzheimers Dis. 2021;80:475–492. doi: 10.3233/JAD-201217. - DOI - PubMed

[5] Seckler J.M., Lewis S.J. Advances in D-Amino Acids in Neurological Research. Int. J. Mol. Sci. 2020;21:7325. doi: 10.3390/ijms21197325. - DOI - PMC - PubMed

[6] Seckler J.M., Lewis S.J. Advances in D-Amino Acids in Neurological Research. Int. J. Mol. Sci. 2020;21:7325. doi: 10.3390/ijms21197325. - DOI - PMC - PubMed

[7] Di Maria E., Bonvicini C., Bonomini C., Alberici A., Zanetti O., Gennarelli M. Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer’s disease. J. Alzheimers Dis. 2009;18:953–960. doi: 10.3233/JAD-2009-1194. - DOI - PubMed

[8] Di Maria E., Bonvicini C., Bonomini C., Alberici A., Zanetti O., Gennarelli M. Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer’s disease. J. Alzheimers Dis. 2009;18:953–960. doi: 10.3233/JAD-2009-1194. - DOI - PubMed

[9] Lin E., Lin C.H., Lai Y.L., Huang C.H., Huang Y.J., Lane H.Y. Combination of G72 Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches. Front. Psychiatry. 2018;9:566. doi: 10.3389/fpsyt.2018.00566. - DOI - PMC - PubMed

[10] Lin E., Lin C.H., Lai Y.L., Huang C.H., Huang Y.J., Lane H.Y. Combination of G72 Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches. Front. Psychiatry. 2018;9:566. doi: 10.3389/fpsyt.2018.00566. - DOI - PMC - PubMed

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d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia

Affiliations

d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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Abstract

Conflict of interest statement

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