NMDA receptor antagonists as potential therapy in cerebellar degenerative disorders

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Abstract

Cerebellar degeneration remains a poorly studied topic. Excitotoxicity, i.e. neuronal damage and death due to excess activation of postsynaptic N-methyl-D-aspartate receptors (NMDAR) by glutamate, is considered to be a universal mechanism of most neurodegenerative conditions. The use of antagonists that predominantly block NMDAR in cases of excitotoxicity is a very promising treatment strategy for neurodegenerative disorders.

This review presents the known structure and function of NMDAR. Information on studies investigating the use of NMDAR antagonists in the treatment of neurodegenerative diseases is provided. Creation of new therapies to correct excitotoxicity in various neurodegenerative disorders, for example, spinocerebellar ataxias, requires further study of the subunit composition and the role of NMDAR in the cerebellum. Treatment methods that combine the use of extrasynaptic NMDAR antagonists or synaptic NMDAR agonists with drugs that affect the total amount of glutamate in the synaptic cleft are promising.

About the authors

Olga S. Belozor

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky

Author for correspondence.
Email: olsbelor@gmail.com
ORCID iD: 0000-0001-8384-5962

assistant, Department of biological chemistry with courses in medical, pharmaceutical and toxicological chemistry

Russian Federation, 660022, Krasnoyarsk, Partizan Zheleznyak str., 1

Andrey N. Shuvaev

Siberian Federal University

Email: olsbelor@gmail.com
ORCID iD: 0000-0002-3887-1413

Associate Professor, Department of biomedical systems and complexes, Institute of Fundamental Biology and Biotechnology

Russian Federation, Krasnoyarsk

Yana V. Fritsler

Siberian Federal University

Email: olsbelor@gmail.com
ORCID iD: 0000-0003-3299-1200

postgraduate student, Department of biophysics, Institute of Fundamental Biology and Biotechnology

Russian Federation, Krasnoyarsk

Anton N. Shuvaev

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky

Email: olsbelor@gmail.com
ORCID iD: 0000-0003-0078-4733

Head, Research Institute of Molecular Medicine and Pathobiochemistry

Russian Federation, 660022, Krasnoyarsk, Partizan Zheleznyak str., 1

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2. Changes in the tricomponent Purkinje cell synapse in neurodegeneration and possible molecular targets for the treatment of cerebellar degeneration. Functioning NMDAR contain the GluN1 subunit, which is why it is not indicated on the image.

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