THE ROLE OF MUTANT GFAP PROTEINS IN THE PATHOGENESIS OF ALEXANDER'S DISEASE: AN INTEGRATIVE REVIEW

• DOI: https://doi.org/10.22533/at.ed.1594632428062

• Palavras-chave: Alexander Disease", "Mutant Protein", "Pathogenesis", "Rare Diseases" and “Glial Fibrillar Acid Protein”.

• Keywords: Alexander Disease", "Mutant Protein", "Pathogenesis", "Rare Diseases" and “Glial Fibrillar Acid Protein”.

• Abstract:

  Objective: To analyze and synthesize the available scientific evidence on the role of the mutant protein GFAP (glial fibrillary acidic protein) in the pathophysiology of Alexander disease. Method: This is an integrative review of the literature, research was carried out using databases available in the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), National Library of Medicine/PubMed, SciELO. The descriptors used were: The descriptors used were: "Alexander's Disease", "Mutant Protein", "Pathogenesis", "Rare Diseases" and “Glial Fibrillar Acid Protein”. Combined with the Boolean operators OR and AND. Results: Studies on Alexander disease emphasize the effects of mutations in the GFAP gene, which cause abnormalities in GFAP intermediate filaments, resulting in excessive aggregation in the astroglial cell. This is associated with mitochondrial dysfunctions, oxidative stress and changes in organelle distribution, contributing to the pathophysiology of the disease, including clinical manifestations such as partial epilepsy continua. Cellular and animal models reveal that such mutations compromise the proper formation of GFAP filaments, leading to the formation of Rosenthal fibers and worsening neurodegeneration. Specific studies such as the R239C mutation indicate that these changes not only impair the structure of the filaments, but also negatively affect the solubility of GFAP, impacting astrocytic function and the integrity of the blood-brain barrier in Alexander disease. Conclusion: The investigation of mutated GFAP proteins in Alexander disease represents a significant advance in clinical neuroscience, highlighting complex molecular pathways involved in pathogenesis. Detailed analysis of the structural and functional changes of these proteins offers crucial insights to overcome diagnostic and therapeutic challenges, essential for improving patients' quality of life and driving the development of new treatments.