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Its prognosis is fatal, with limited treatment options currently available. The GFAP protein is a marker for mature astrocytes. It results in the upregulation of reactive astroglioses. Reactive astroglioses is a neuroprotective condition that, when functioning correctly, helps protect the brain from stress and injury and prevents further injury. However, unregulated reactive astroglioses is linked with many neurodegenerative diseases. Due to the relative rarity in the incidence of AxD, treatment options have not been as widely investigated. This review explores potential drug targets that may impact GFAP gene expression, such as STAT3, GDNF, NF-kB, LCN-2, and the LPS pathway. These drug targets have previously been or are currently being explored in other neurodegenerative diseases such as Parkinson\u2019s disease and Alzheimer\u2019s disease. The only treatment option currently in clinical trial phases involves methods to induce the knockout of the GFAP gene. Due to GFAP\u2019s neuroprotective role in brain injury and stress, it is important to explore alternative treatment options that downregulate GFAP as opposed to shutting it off entirely.<\/jats:p>","DOI":"10.1007\/s12035-025-05083-1","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T02:12:39Z","timestamp":1748657559000},"page":"15010-15023","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alexander\u2019s Disease: Potential Drug Targets and Future Directions"],"prefix":"10.1007","volume":"62","author":[{"given":"Emily","family":"Zavala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahl","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"5083_CR1","doi-asserted-by":"publisher","unstructured":"Pajares MA, Hern\u00e1ndez-Gerez E, Pekny M, P\u00e9rez-Sala D (2023) Alexander disease: the road ahead. 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