en Cell, Stem Cell and Cancer Cell, Stem Cell and Cancer Experimental research article Experimental research article <p dir="ltr" style="text-align: justify;"><span style="font-size:11px;">Introduction: Neurodegenerative diseases are progressive disorders that could impair neuronal functions and structures. Oxidative stress and mitochondrial dysfunction are involved in the etiology of neurodegenerative diseases such as Alzheimer&rsquo;s disease, Parkinson&rsquo;s disease and etc. Gemfibrozil is used as a therapeutic drug for hyperlipidemia. It has been shown that gemfibrozil is neuroprotective via modulation of mitochondrial biogenesis pathway under oxidative stress condition and in a sex-dependent manner.&nbsp;Materials and Methods: In this study, neuronal-like PC12 cells with were pretreated with different concentrations of gemfibrozil and H2O2, concomitantly.&nbsp;Results: In gemfibrozil pretreated groups, reduced level of caspase-3 and raised mitochondrial transcription factor A (TFAM) levels were detected. In contrast, adding fulvestrant, an Estradiol receptor antagonist, prevents the impact of gemfibrozil on oxidative stress condition, reducing its efficacy to protect the neurons against stress.&nbsp;Conclusion: Our results indicated the involvement of estradiol receptors in gemfibrozil neuroprotective mechanism, in diminishing oxidative stress-induced damage via reducing caspase-3 and inducing the level of TFAM that plays a crucial role in the mitochondrial biogenesis.</span></p> Gemfibrozil, Mitochondrial transcription factor A, Fulvestrant, Caspase 3, H2O2 253 262 http://ppj.phypha.ir/browse.php?a_code=A-10-881-2&slc_lang=en&sid=1 Ghorbangol Ashabi as_habi@yahoo.com 3200319475328460015845 3200319475328460015845 No Physiology Research Center and Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Leila Khalaj lkhalaj@yahoo.com 3200319475328460015846 3200319475328460015846 Yes Medical School, Alborz University of Medical Sciences, Alborz, Iran