These observations indicate that curcumin rescued synaptic activity from A induced toxicity. Curcumin+A In cells pretreated with curcumin and incubated with A relative to untreated cells, mRNA levels were increased for synaptophysin by 1.2 fold and 1.1 fold for PSD95, indicating that curcumin prevented A induced synaptic activity. Comparison with A treated cells As shown in table 4, mRNA levels of fission genes were reduced in cells treated with A+curcumin (Drp1 by 1.7 fold, p=0.02; Fis1 by 1.8 fold, p=0.002) and curcumin+A (Drp1 by 1.6 fold, p=0.02; Fis1 by 2.2 fold, p=0.003) relative to A treated cells. In contrast, fusion genes were increased in A+curcumin (Mfn1 by 2.8 fold, p=0.003; Mfn2 by 1.6 fold, p=0.03; Opa1 Cav 2.2 blocker 1 by 1.6, p=0.03) and curcumin+A (Mfn1 by 3.8 fold, p=0.002; Mfn2 by 1.9 fold, p=0.01; Opa1 by 2.2 fold, p=0.002) treated cells relative to A treated cells. Mitochondrial biogenesis genes were increased in A+curcumin (PGC1 by 1.5 fold, p=0.04; Nrf1 by 1.6 fold, p=0.03; Nrf2 by 1.9 fold, p=0.01; and TFAM by 1.8 fold, p=0.03) and curcumin+A (PGC1 by 1.8 fold, p=0.03; Nrf1 by 2.2 fold, p=0.002; Nrf2 by 2.3 fold, p=0.002; and TFAM by 1.8 fold, p=0.02) treated cells relative to A treated cells. Similar to biogenesis genes, synaptic genes were increased in A+curcumin (synaptophysin by 3.2 fold, p=0.002; PSD95 by 1.6 fold, p=0.04) and curcumin+A (synaptophysin 2.6 fold, p=0.004; PSD95 by 1.9 fold, p=0.03) treated cells relative to A treated cells (table 4). Immunoblotting analysis To determine the effects of A on mitochondrial proteins and the useful effects of curcumin at the protein level, we quantified mitochondrial proteins in three independent treatments of cells with A, curcumin, A+curcumin and curcumin+A. Comparison with untreated cells A In SHSY5Y cells treated with A compared with untreated SHSY5Y cells, significantly increased proteins levels were found for Drp1 (p=0.02) and Fis1 (p=0.04) (figure 2A, B). by measuring hydrogen peroxide, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP. Cell viability was studied using the MTT assay. A was found to impair mitochondrial dynamics, reduce mitochondrial biogenesis and decrease synaptic activity and mitochondrial function. In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial function and cell viability were elevated in curcumin treated cells. Interestingly, curcumin pre- and post-treated cells incubated with A showed reduced mitochondrial dysfunction, and maintained cell viability and mitochondrial dynamics, mitochondrial biogenesis and synaptic activity. Further, the protective effects of curcumin were stronger in pretreated SHSY5Y cells than in post-treated cells, indicating that curcumin works better in prevention than treatment in AD-like neurons. Our findings suggest that curcumin is a promising drug molecule to treat AD patients. strong class=”kwd-title” Keywords: Aging, Alzheimer Disease, Antioxidants Introduction Alzheimer’s disease (AD) is the most common form of dementia in elderly individuals and is the sixth leading cause of death in the USA. AD is an age dependent and progressive neurodegenerative disease, characterized by the loss of memory, cognitive functions, and changes in behavior and personality.1C3 According to the 2015 World Alzheimer Report, it was estimated that 47.5 million people have dementia worldwide, and the numbers are estimated to increase to 75.6 million by 2030 and to 131.5 million by 2050. Dementia has a huge economic impact, and the 2015 total estimated healthcare cost is about US$818 billion and estimated to increase to US$2 trillion by 2015.4 Causal factors are known for AD for a small proportion (1C2%) of total AD patients, and causal factors are still unknown for the vast majority of AD cases. Several risk factors have been identified, the major one being ApoE4 genotype Rabbit polyclonal to ADORA1 and polymorphisms in several genetic loci, including sortilin related receptor 1, clusterin, complement component receptor 1, CD2AP, CD33, Cav 2.2 blocker 1 and EPHA1, and MS4A4/MS4A6E genes are other contributing risk factors.5 In addition, type 2 diabetes, traumatic brain injury, stroke and diet, and environmental factors are other contributing factors. Above all, ageing is the number one risk factor. Several years of research revealed that AD is associated with multiple cellular changes, including mitochondrial harm, lack of synapses, amyloid (A) development and accumulation, activation of astrocytes and microglia, phosphorylation of tau and neurofibrillary tangles reduction and development of neurons.1C3 Therapeutic strategies have already been developed predicated on these mobile changes and becoming tested in preclinical (animal choices) and human being clinical trials. Nevertheless, we don’t have drugs/agents that may hold off and/or prevent disease development of Advertisement. Further, we still don’t have early detectable biomarkers that may identify cognitive memory and decrease problems in seniors individuals. Physical activity and healthy diet programs have already been reported to possess implications in delaying disease development of Advertisement in elderly people and improved cognitive function in topics with gentle cognitive impairment and early Advertisement patients.6 Natural basic products are the key source of diet programs which have multiple neuroprotective results, including anti-inflammatory, antioxidant, memory space and anti-arthritis cognitive features. 7C9 There are always a large numbers of organic herbal products and items available, including curcumin, green tea extract and supplement C, supplement E, carotene, Gingko biloba, ginseng, rosemary, sage and many more.6C9 As the primary theme of the special topic is natural basic products, Cav 2.2 blocker 1 in today’s study, we researched the protective ramifications of curcumin against A induced toxicities in the pathogenesis of AD. Curcumin may be the main constituent from Cav 2.2 blocker 1 the Asian spice, turmeric, isolated through the rhizome of Curcuma longa.10 11 Curcumin was isolated in 1815 like a yellow coloring matter through the rhizomes of Curcuma longa (turmeric)12 and named curcumin. Curcumin continues to be utilized historically in Ayurvedic medication (curcumin can be popularly known as Haldi in India and its own chemical name can be diferuloylmethane; molecular method can be C21H20O6). It molecular mass can be.