The Role of Alpha-Synuclein in Neurodevelopmental Diseases

doi:10.1007/s12035-024-04305-2

Review

. 2025 Jan;62(1):962-972.

doi: 10.1007/s12035-024-04305-2. Epub 2024 Jun 29.

The Role of Alpha-Synuclein in Neurodevelopmental Diseases

Sanaz Bordbar^{1

2}, Dorsa Alijanzadeh^{2

3

4}, Noosha Samieefar^{2

3

4}, Mohammad Amin Khazeei Tabari^{2

5

6}, Elham Pourbakhtyaran^{2

3

7}, Nima Rezaei^{8

9

10}

Affiliations

¹ Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, 1417755331, Iran.
² Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
³ School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ USERN Office, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ USERN Office, Mazandaran University of Medical Sciences, Sari, Iran.
⁷ Department of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir.
⁹ Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Dr. Qarib St., Keshavarz Blvd, Tehran, 14194, Iran. rezaei_nima@tums.ac.ir.
¹⁰ Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir.

PMID: 38949729
DOI: 10.1007/s12035-024-04305-2

Review

The Role of Alpha-Synuclein in Neurodevelopmental Diseases

Sanaz Bordbar et al. Mol Neurobiol. 2025 Jan.

. 2025 Jan;62(1):962-972.

doi: 10.1007/s12035-024-04305-2. Epub 2024 Jun 29.

Authors

Sanaz Bordbar^{1

2}, Dorsa Alijanzadeh^{2

3

4}, Noosha Samieefar^{2

3

4}, Mohammad Amin Khazeei Tabari^{2

5

6}, Elham Pourbakhtyaran^{2

3

7}, Nima Rezaei^{8

9

10}

Affiliations

¹ Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, 1417755331, Iran.
² Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
³ School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁴ USERN Office, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ USERN Office, Mazandaran University of Medical Sciences, Sari, Iran.
⁷ Department of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir.
⁹ Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Dr. Qarib St., Keshavarz Blvd, Tehran, 14194, Iran. rezaei_nima@tums.ac.ir.
¹⁰ Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir.

PMID: 38949729
DOI: 10.1007/s12035-024-04305-2

Abstract

Neurodevelopmental disorders are a group of diseases with cognitive, motor, and emotional development deficits. Alpha-synuclein (α-syn) is a synaptic protein involved in transmission and neurodevelopment. This protein was previously shown to be associated with several disorders, including Parkinson's disease. Furthermore, a close link between neurodevelopmental disorders and Parkinson's has also been found. Changes in synaptic function have been noticed in neurodevelopmental disorders, including autism spectrum disorder. Impaired neurogenesis and related cognitive problems have been associated with altered expression of α-syn. Various studies reported α-syn in different body fluids and tissues such as blood and serum. Alpha-synuclein can help in better understanding the pathogenesis of neurodevelopmental diseases and facilitating their early diagnosis. This review aims to go over the recent advances in the role of α-syn in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, and motor and social impairment, and its value as a diagnostic biomarker.

Keywords: Alpha-synuclein; Attention deficit hyperactivity disorder; Autism spectrum disorder; Neurodevelopmental disorders.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests.

References

1. Dsm IV (1994) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC, vol 968, pp 33–36
1. Yang Y, Zhao S, Zhang M, Xiang M, Zhao J, Chen S, Wang H, Han L et al (2022) Prevalence of neurodevelopmental disorders among US children and adolescents in 2019 and 2020. Front Psychol 13:997648. https://doi.org/10.3389/fpsyg.2022.997648 - DOI - PubMed - PMC
1. Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A et al (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 68(11):1095–1102. https://doi.org/10.1001/archgenpsychiatry.2011.76 - DOI - PubMed - PMC
1. Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E et al (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506(7487):179–184. https://doi.org/10.1038/nature12929 - DOI - PubMed - PMC
1. Nisar S, Haris M, Fakhro KA (2022) Genes and specific (related) proteins in neurodevelopmental disorders. In: Qoronfleh MW, Essa MM, Saravana Babu C (eds) Proteins Associated with neurodevelopmental disorders. Springer Singapore, Singapore, pp 49–89. https://doi.org/10.1007/978-981-15-9781-7_2

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[1] Dsm IV (1994) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC, vol 968, pp 33–36

[2] Dsm IV (1994) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC, vol 968, pp 33–36

[3] Yang Y, Zhao S, Zhang M, Xiang M, Zhao J, Chen S, Wang H, Han L et al (2022) Prevalence of neurodevelopmental disorders among US children and adolescents in 2019 and 2020. Front Psychol 13:997648. https://doi.org/10.3389/fpsyg.2022.997648 - DOI - PubMed - PMC

[4] Yang Y, Zhao S, Zhang M, Xiang M, Zhao J, Chen S, Wang H, Han L et al (2022) Prevalence of neurodevelopmental disorders among US children and adolescents in 2019 and 2020. Front Psychol 13:997648. https://doi.org/10.3389/fpsyg.2022.997648 - DOI - PubMed - PMC

[5] Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A et al (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 68(11):1095–1102. https://doi.org/10.1001/archgenpsychiatry.2011.76 - DOI - PubMed - PMC

[6] Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A et al (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 68(11):1095–1102. https://doi.org/10.1001/archgenpsychiatry.2011.76 - DOI - PubMed - PMC

[7] Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E et al (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506(7487):179–184. https://doi.org/10.1038/nature12929 - DOI - PubMed - PMC

[8] Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E et al (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506(7487):179–184. https://doi.org/10.1038/nature12929 - DOI - PubMed - PMC

[9] Nisar S, Haris M, Fakhro KA (2022) Genes and specific (related) proteins in neurodevelopmental disorders. In: Qoronfleh MW, Essa MM, Saravana Babu C (eds) Proteins Associated with neurodevelopmental disorders. Springer Singapore, Singapore, pp 49–89. https://doi.org/10.1007/978-981-15-9781-7_2

[10] Nisar S, Haris M, Fakhro KA (2022) Genes and specific (related) proteins in neurodevelopmental disorders. In: Qoronfleh MW, Essa MM, Saravana Babu C (eds) Proteins Associated with neurodevelopmental disorders. Springer Singapore, Singapore, pp 49–89. https://doi.org/10.1007/978-981-15-9781-7_2

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The Role of Alpha-Synuclein in Neurodevelopmental Diseases

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The Role of Alpha-Synuclein in Neurodevelopmental Diseases

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