Nicotinic acid attenuates amyloid ß1-42-induced mitochondrial dysfunction and inhibits the mitochondrial pathway of apoptosis in differentiated SH-SY5Y cells.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and behavioral disorders. The excessive accumulation of amyloid ß (Aß) and the formation of neurofibrillary tangles (NFTs) damage synaptic connections and the death of neurons. However, the underlying mechanisms of pathogenesis of AD remain unclear. Growing evidence indicates that impaired mitochondrial function may play a crucial role in the development of AD. In the current study, we investigated whether nicotinic acid (NA) could protect against amyloid ß1-42-induced cytotoxicity in differentiated SH-SY5Y cells. Our results revealed the neuroprotective effects of NA on the differentiated SH-SY5Y cells treated with Aß1-42. In detail, the 1-h pre-incubation with NA increased cell viability and lowered LDH levels. NA pre-incubation abolished Aß1-42 treatment-associated alterations of mRNA levels of synaptic genes and enhanced the relative ß3 Tubulin fluorescence intensity. NA eliminated the Aß1-42-induced mitochondrial dysfunction by increasing the potential of mitochondrial membranes and maintaining a balance between the fusion and fission of mitochondria. Moreover, Aß1-42 decreased mRNA levels of anti-apoptotic bcl2 and increased mRNA levels of pro-apoptotic: bim, bak, cytochrome c, and caspase 9. At the same time, the NA pre-treatment reduced Aß1-42-dependent apoptotic death of differentiated SH-SY5Y cells. The above data suggest that NA presents a protective activity against Aß1-42-induced cytotoxicity in differentiated SH-SY5Y cells by inhibiting the mitochondrial pathway of apoptosis and restoring the proper function of mitochondria.

Obesity as a Risk Factor for Breast Cancer-The Role of miRNA.

Breast cancer (BC) is the most common cancer diagnosed among women in the world, with an ever-increasing incidence rate. Due to the dynamic increase in the occurrence of risk factors, including obesity and related metabolic disorders, the search for new regulatory mechanisms is necessary. This will help a complete understanding of the pathogenesis of breast cancer. The review presents the mechanisms of obesity as a factor that increases the risk of developing breast cancer and that even initiates the cancer process in the female population. The mechanisms presented in the paper relate to the inflammatory process resulting from current or progressive obesity leading to cell metabolism disorders and disturbed hormonal metabolism. All these processes are widely regulated by the action of microRNAs (miRNAs), which may constitute potential biomarkers influencing the pathogenesis of breast cancer and may be a promising target of anti-cancer therapies.

Contribution of Mitochondrial Dysfunction Combined with NLRP3 Inflammasome Activation in Selected Neurodegenerative Diseases.

Alzheimer's disease and Parkinson's disease are the most common forms of neurodegenerative illnesses. It has been widely accepted that neuroinflammation is the key pathogenic mechanism in neurodegeneration. Both mitochondrial dysfunction and enhanced NLRP3 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 3) inflammasome complex activity have a crucial role in inducing and sustaining neuroinflammation. In addition, mitochondrial-related inflammatory factors could drive the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). The present review includes a broadened approach to the role of mitochondrial dysfunction resulting in abnormal NLRP3 activation in selected neurodegenerative diseases. Moreover, we also discuss the potential mitochondria-focused treatments that could influence the NLRP3 complex.

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer's disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer's disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer's disease.

All-trans-retinoic acid ameliorates atherosclerosis, promotes perivascular adipose tissue browning, and increases adiponectin production in Apo-E mice.

All-trans-retinoic acid (atRA), an active metabolite of vitamin A, exerts a potential role in the prevention of cardiovascular diseases. It has been shown that atRA ameliorates atherosclerosis while the exact mechanism underlying this protection remains unknown. This study investigated the influence of atRA on insulin resistance (IR), atherosclerosis, and the process of perivascular adipose tissue (PVAT) browning. Moreover, syntheses of adiponectin, adipokine with anti-atherogenic effects, and tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, were determined in PVAT. Apolipoprotein E-deficient mice (Apo-E) and control C57BL/6J wild-type mice were treated with atRA (5 mg/kg/day) or vehicle (corn oil) by plastic feeding tubes for 8 weeks. Long-term atRA treatment in Apo-E mice did not affect insulin resistance. AtRa administration ameliorated atherosclerosis, induced PVAT browning, and increased adiponectin production in PVAT in Apo-E mice. Furthermore, atRA increased nitric oxide (NO) level but did not affect adiponectin concentration in the aorta of Apo-E mice. These results indicate that atRA ameliorates atherosclerosis in Apo-E mice. We also observed the browning of PVAT. Besides, atRA increased the synthesis of adiponectin in PVAT and augmented NO level in the aorta in ApoE mice.

The Effects of Alpha-Linolenic Acid on the Secretory Activity of Astrocytes and ß Amyloid-Associated Neurodegeneration in Differentiated SH-SY5Y Cells: Alpha-Linolenic Acid Protects the SH-SY5Y cells against ß Amyloid Toxicity.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid ß- (Aß-) induced mitochondrial dysfunction may be a primary process triggering all the cascades of events that lead to AD. Therefore, identification of natural factors and endogenous mechanisms that protect neurons against Aß toxicity is needed. In the current study, we investigated whether alpha-linolenic acid (ALA), as a natural product, would increase insulin and IGF-I (insulin-like growth factor I) release from astrocytes. Moreover, we explored the protective effect of astrocytes-derived insulin/IGF-I on Aß-induced neurotoxicity, with special attention paid to their impact on mitochondrial function of differentiated SH-SY5Y cells. The results showed that ALA induced insulin and IGF-I secretion from astrocytes. Our findings demonstrated that astrocyte-derived insulin/insulin-like growth factor I protects differentiated SH-SY5Y cells against Aß 1-42-induced cell death. Moreover, pretreatment with conditioned medium (CM) and ALA-preactivated CM (ALA-CM) protected the SH-SY5Y cells against Aß 1-42-induced mitochondrial dysfunction by reducing the depolarization of the mitochondrial membrane, increasing mitochondrial biogenesis, restoring the balance between fusion and fission processes, and regulation of mitophagy and autophagy processes. Our study suggested that astrocyte-derived insulin/insulin-like growth factor I suppresses Aß 1-42-induced cytotoxicity in the SH-SY5Y cells by protecting against mitochondrial dysfunction. Moreover, the neuroprotective effects of CM were intensified by preactivation with ALA.