Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. Lysophosphatidic acid (LPA, small extracellular-signaling molecule) is elevated in ischemic stroke and traumatic brain injury. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Hence, the aim of this study is to investigate whether LPA might promote AD pathology through mitochondrial dysfunction, oxidative stress, and apoptosis. Additionally, we will investigate whether atorvastatin could attenuate LPA-induced neurotoxicity. SHSY-5Y cells were treated with retinoic acid to achieve neuronal phenotype. Neuronal viability was measured using MTT assay. Time dependent effect (6, 12, 24 hours) of LPA (10uM) induces the apoptosis (increased caspase 3 activity) of differentiated SHSY-5Y cells through mitochondrial dysfunction (decreased Complex I and Complex IV activity), oxidative stress (increased ROS, lipid peroxide & decreased glutathione content). Furthermore, we will investigate the neuroprotective effects of Atorvastatin (HMG-CoA reductase inhibitors) on LPA-induced oxidative stress, apoptosis, and mitochondrial dysfunction by evaluating the markers of oxidative stress, apoptosis, and mitochondrial function. Exploration of the multitude of mitochondrial and apoptotic mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease.