{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:50:41Z","timestamp":1785408641778,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"John J And Marjorie M Passan Foundation"},{"DOI":"10.13039\/100010473","name":"Alzheimer\u2019s Foundation of America","doi-asserted-by":"publisher","award":["AWD00004772"],"award-info":[{"award-number":["AWD00004772"]}],"id":[{"id":"10.13039\/100010473","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AWD00004772"],"award-info":[{"award-number":["AWD00004772"]}],"id":[{"id":"https:\/\/ror.org\/03tkh8741","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Herb and Evelyn Abrams Family Amyloid Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background and Objectives: Cornerstone therapies for metastatic prostate cancer include androgen deprivation and androgen receptor pathway inhibition, but cognitive impairment is a recognized, life-altering potential adverse effect of this treatment. Abiraterone acetate (AA), an androgen receptor pathway and CYP17A1 inhibitor, suppresses androgen synthesis and may contribute to cognitive changes. This cell culture-based study uses the BE(2)M17 human male neuroblastoma model to investigate AA-induced alterations in gene and protein expression that may underlie cognitive decline, laying the foundation for a mechanistic investigation aimed at identifying molecular targets to mitigate cognitive impairment in men with prostate cancer receiving androgen-directed therapies. Materials and Methods: BE(2)M17 cells were pretreated for 12 h with dihydrotestosterone (DHT; 5 nM) or vehicle control, then exposed to AA (0, 5, 10 \u00b5M, 24 h). RNA and protein were analyzed by qRT-PCR and Western blot for markers of amyloid processing, neuronal health, and mitochondrial function. Results: AA significantly altered multiple neurobiological markers. BACE1 mRNA increased in DHT + 10 \u00b5M AA compared to control and DHT alone (p = 0.0416 and p = 0.0118). However, BACE1 protein decreased in 10 \u00b5M AA + DHT versus DHT alone (p = 0.0132). Immunoblot revealed reduced amyloid precursor protein (APP) in 10 \u00b5M AA versus control (p = 0.0057) and 10 \u00b5M versus 5 \u00b5M (p = 0.0263). APP was reduced in 10 \u00b5M AA + DHT versus control (p = 0.0015) and versus DHT alone (p = 0.0467). LRP1 and BDNF were significantly reduced with 10 \u00b5M AA versus 5 \u00b5M AA (p = 0.0092 and p = 0.0081), while synaptophysin decreased in 10 \u00b5M AA + DHT versus DHT alone (p = 0.0049). BDNF also declined in 10 \u00b5M AA + DHT compared to 5 \u00b5M AA + DHT (p = 0.0301). PGC1\u03b1 mRNA increased in AA + DHT versus DHT alone (p = 0.0332). MitoTracker analysis showed reduced fluorescence with 5 \u00b5M AA alone but increased fluorescence with 5 \u00b5M AA + DHT relative to control and DHT (p = 0.0019; p &lt; 0.0001), while 10 \u00b5M AA + DHT reduced fluorescence compared to 5 \u00b5M AA + DHT (p = 0.0003). Conclusions: AA, alone or combined with DHT, disrupts key pathways involved in neuronal health, amyloid processing, and mitochondrial function. These findings suggest a potential mechanistic link between AA treatment and cognitive impairment.<\/jats:p>","DOI":"10.3390\/life16071184","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:55:59Z","timestamp":1784249759000},"page":"1184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abiraterone Acetate Affects Gene Expression Profile in a Human Male Neuronal Cell Line: Potential Mechanism for Cognitive Deficits with Prostate Cancer Therapy"],"prefix":"10.3390","volume":"16","author":[{"given":"Shelly","family":"Gulkarov","sequence":"first","affiliation":[{"name":"Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4478-2441","authenticated-orcid":false,"given":"Allison B.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"},{"name":"Department of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-2183","authenticated-orcid":false,"given":"Ankita","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Lim-Goyette","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Renna","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-8188","authenticated-orcid":false,"given":"Andrew","family":"Laccetti","sequence":"additional","affiliation":[{"name":"Department of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron E.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Urology, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Reiss, A.B., Gulkarov, S., Pinkhasov, A., Sheehan, K.M., Srivastava, A., De Leon, J., and Katz, A.E. 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