NEUROINFLAMMATION MECHANISMS, CLINICAL IMPLICATIONS, AND THERAPEUTIC APPROACHES

neuroinflamationkapak

NEUROINFLAMMATION IN AMYOTROPHIC LATERAL SCLEROSIS: DUAL ROLE, MECHANISMS, AND THERAPEUTIC IMPLICATIONS

Duygu Aydemir1 Nuriye Nuray Ulusu2 Barış İşak3

1Koç University, Faculty of Medicine, Department of Medical Biochemistry; Koç University Research Center for Translational Medicine (KUTTAM); İstanbul University, Institute of Child Health, Department of Pediatric Basic Sciences, Division of Medical Genetics, İstanbul, Türkiye
2Koç University, Faculty of Medicine, Department of Medical Biochemistry; Koç University Research Center for Translational Medicine (KUTTAM) İstanbul, Türkiye
3Marmara University, Faculty of Medicine, Department of Neurology, İstanbul, Türkiye

Aydemir D, Ulusu NN, İşak B. Neuroinflammation in Amyotrophic Lateral Sclerosis: Dual Role, Mechanisms, and Therapeutic Implications. In: Şahin Ş editor. Neuroinflammation. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.109-123.

ABSTRACT

Neuroinflammation is increasingly recognized as a complex contributor to amyotrophic lateral sclerosis (ALS) pathogenesis. Yet, whether neuroinflammation acts as a causative factor or a consequence of motor neuron degeneration remains uncertain. Neuroinflammation plays a dual role in ALS where early-stage anti-inflammatory responses promote neuronal survival, but late-stage pro-inflammatory states exacerbate neuronal damage. Key mediators include microglia, astrocytes, and peripheral immune cells, whose phenotypic shifts significantly influence disease progression. Genetic factors such as SOD1, C9orf72, TDP43, and FUS mutations further exacerbate these inflammatory pathways. This chapter comprehensively discusses neuroinflammation in ALS based on the underlying molecular and cellular mechanisms and evidence from clinical studies and drug trials. Novel interventions targeting inflammatory pathways, including immune-modulatory drugs, stem cell transplantation, and off-label treatments, hold promise but face challenges due to ALS’s heterogeneity and dynamic inflammatory states. The review also highlights innovations in preclinical models and biomarker identification, pivotal for understanding disease mechanisms and personalizing therapeutic strategies. Future research must prioritize resolving the complexities of neuroinflammatory responses, tailoring interventions to individual genetic profiles, and optimizing treatment timing to address ALS’s multifaceted pathology.

Keywords: Amyotrophic lateral sclerosis; Oxidative stress; Gliosis; Biomarkers; Immunotherapy

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