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In alignment with that, we investigated the natural history of KD spanning eight decades to gain a deeper understanding of the evolutionary trajectory of its mechanisms. Through our comprehensive analysis, we unearthed additional novel elements in molecular biology involving the micropathological mechanism of the disease. This review offers an updated perspective on the metabolic disorder that defines KD. Recently, extracellular vesicles (EVs), autophagy impairment, and \u03b1\u2010synuclein have emerged as pivotal players in the neuropathological processes. EVs might serve as a cellular mechanism to avoid or alleviate the detrimental impacts of excessive toxic psychosine levels, and extracting EVs could contribute to synapse dysfunction. Autophagy impairment was found to be independent of psychosine and reliant on AKT and B\u2010cell lymphoma 2. Additionally, \u03b1\u2010synuclein has been recognized for inducing cellular death and dysfunction in common biological pathways. Our objective is to assess the effectiveness of advanced therapies in addressing this particular condition. While hematopoietic stem cells have been a primary treatment, its administration proves challenging, particularly in the presymptomatic phase. In this review, we have compiled information from over 10 therapy trials, comparing them based on their benefits and disadvantage.<\/jats:p>","DOI":"10.1111\/neup.12967","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T08:04:39Z","timestamp":1709712279000},"page":"255-277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["From pathological mechanisms in Krabbe disease to cutting\u2010edge therapy: A comprehensive review"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-8028","authenticated-orcid":false,"given":"Imen","family":"Ketata","sequence":"first","affiliation":[{"name":"Neurology Department University Hospital of Gabes  Gabes Tunisia"},{"name":"Sfax University, Sfax Faculty of Medicine  Sfax 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