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It remains the primary neuropathological criteria for the diagnosis of AD. Additionally, several other processes are currently being recognized as significant risk factors for AD development, including the brain's susceptibility to reactive oxygen species (ROS). The ROS production is among the early signs in the progression of AD. However, the underlying mechanisms behind increased ROS production in AD remain poorly understood. We have observed SNTA1 plays critical role in regulating ROS levels in different pathological conditions. Here, we wanted to gain further insight into the role of SNTA1 in the development of AD by using IMR32 cell line. Our results show that the accumulation of A\u03b2 plaques in Alzheimer's model neuroblastoma cells significantly increases the expression and activation of SNTA1 and MKK6 kinase. The activation of MKK6 results in the phosphorylation of SNTA1, creating a binding site for Rac1, leading to its activation and subsequent production of ROS. Excessive ROS production leads to cell cycle arrest in the G2\/M phase, a hallmark of AD. Our study provides new insight into the mechanism of A\u03b2\u2010mediated cell death in AD and suggests that MKK6\u2010mediated activation of alpha\u20101\u2010syntrophin promotes ROS production in neuronal cells, resulting in cell death. This study presents a mechanistic insight into A\u03b2\u2010mediated cell death and could serve as a paradigm for reducing neuronal cell death in AD.<\/jats:p>","DOI":"10.1111\/ejn.16609","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T01:45:03Z","timestamp":1731635103000},"page":"6935-6952","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Amyloid beta\u2013activated alpha\u20101\u2010syntrophin has ramifications on Rac1 activation, ROS production and neuronal cell death"],"prefix":"10.1111","volume":"60","author":[{"given":"Umar","family":"Mushtaq","sequence":"first","affiliation":[{"name":"Department of Biotechnology University of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rais A.","family":"Ganai","sequence":"additional","affiliation":[{"name":"Watson\u2010Crick Centre for Molecular Medicine Islamic University 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