The role of neuroinflammation and impairment of the blood-spinal cord barrier in pathogenesis of amyotrophic lateral sclerosis

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons in the brain and spinal cord. As the disease progresses, paralysis and skeletal muscle atrophy develop, ultimately leading to fatal outcomes. Investigation of ALS pathogenetic mechanisms is crucial for developing effective treatment approaches. This literature review examines the role of neuroinflammation and blood-spinal cord barrier dysfunction in disease progression. Damaged neurons release proinflammatory cytokines as the pathology advances. Neuroinflammation in ALS develops through activation of the NF-κB pathway and cGAS/STING pathway, RNA metabolism dysregulation, microglial and astrocyte activation/proliferation, immune cell involvement, and other processes. Activated astrocytes and microglia increase blood-spinal cord barrier permeability. Neuroinflammation induces endothelial mitochondrial dysfunction, capillary diameter reduction, and progressive loss of perivascular components. The complex of proinflammatory reactions affecting central nervous system barriers accelerates ALS symptom progression. This review presents current data and analysis of pathogenetic mechanisms underlying neuroinflammation and blood-spinal cord barrier disruption in ALS.

About the authors

Egor S. Averchuk

Russian Center of Neurology and Neurosciences

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-5736-4636

postgraduate student

Russian Federation, Moscow

Alla B. Salmina

Russian Center of Neurology and Neurosciences

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0003-4012-6348

D. Sci. (Med.), Corresponding member of RAS, Prof., chief researcher, Head, Laboratory of neurobiology and tissue engineering, Brain Institute

Russian Federation, Moscow

Liaisan A. Akhmadieva

Kazan State Medical University

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0009-0000-4926-3192

junior researcher, Institute of Neuroscience

Russian Federation, Kazan

Marat A. Mukhamedyarov

Kazan State Medical University

Author for correspondence.
Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-0397-9002

D. Sci. (Med.), Prof. Head, Department of normal physiology, Director, Institute of Neuroscience

Russian Federation, Kazan

Sergey N. Illarioshkin

Russian Center of Neurology and Neurosciences

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-2704-6282

Dr. Sci. (Med.), Prof., Full member of the RAS, Director, Brain Institute, Deputy director, Russian Center

Russian Federation, Moscow

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