Alzheimer's disease (AD) is a neurodegenerative disorder and its reported pathophysiological features in the brain include the deposition of amyloid beta peptide, chronic inflammation, and cognitive impairment. The incidence of AD is increasing worldwide and researchers have studied various aspects of AD pathophysiology in order to improve our understanding of the disease. Thus far, the onset mechanisms and means of preventing AD are completely unknown. Peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) is a protein related to various cellular mechanisms that lead to the alteration of downstream gene regulation. It has been reported that PGC-1α could protect cells against oxidative stress and reduce mitochondrial dysfunction. Moreover, it has been demonstrated to have a regulatory role in inflammatory signaling and insulin sensitivity related to cognitive function. Here, we present further evidence of the involvement of PGC-1α in AD pathogenesis. Clarifying the relationship between PGC-1α and AD pathology might highlight PGC-1α as a possible target for therapeutic intervention in AD.
Alzheimer Disease* ; Amyloid beta-Peptides ; Brain ; Incidence ; Inflammation ; Insulin Resistance ; Neurodegenerative Diseases ; Oxidative Stress ; Pathology ; Peroxisomes

Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, Type 2 diabetes, obesity and also in the neurodegenerative disorders including Alzheimer's disease. Adiponectin regulates the sensitivity of insulin, fatty acid catabolism, glucose homeostasis and anti-inflammatory system through various mechanisms. Previous studies demonstrated that adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimer's disease. Here, we aim to summarize recent studies that suggest the potential correlation between adiponectin and Alzheimer's disease.
Adiponectin* ; Adipose Tissue ; Alzheimer Disease* ; Cardiovascular Diseases ; Glucose ; Homeostasis ; Immune System ; Insulin ; Memory ; Metabolism ; Neurodegenerative Diseases ; Obesity

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau protein in the brain, leading to the increase in inflammation and neuronal loss. Recently, evidences to support the association between type 2 diabetes mellitus (T2DM) and AD have markedly increased by clinical researches and experimental studies. Reduced insulin action and impaired glucose metabolism in the brain leads to diabetes induced AD. Androgen, a male sex hormone, was known to regulate inflammatory response, Aβ deposition in AD, insulin signaling, and synaptic plasticity in brain. Clinical studies demonstrated that androgen deficiency results in the increased risk of AD and its severe progression in male subjects. We reviewed the significant evidences to support that low testosterone levels are linked to diabetes-induced AD based on previous studies. Thus, we highlight the therapeutic potential of androgen in diabetes induced AD.
Alzheimer Disease* ; Amyloid ; Brain ; Diabetes Mellitus, Type 2 ; Glucose ; Humans ; Inflammation ; Insulin ; Insulin Resistance ; Male ; Metabolism ; Neuronal Plasticity ; Neurons ; tau Proteins ; Testosterone

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.
Brain ; Cognition ; Dementia, Vascular ; Energy Metabolism ; Fasting ; Glucose ; Insulin Resistance ; Life Style ; Metabolism ; Methods ; Pathology ; Risk Factors

Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily was reported to participate in various biological processes including cell migration, cell survival, inflammatory responses, and insulin sensitivity. LCN2 is expressed in the multiple tissues such as kidney, liver, uterus, and bone marrow. The receptors for LCN2 were additionally found in microglia, astrocytes, epithelial cells, and neurons, but the role of LCN2 in the central nervous system (CNS) has not been fully understood yet. Recently, in vitro, in vivo, and clinical studies reported the association between LCN2 and the risk of Alzheimer's disease (AD). Here, we reviewed the significant evidences showing that LCN2 contributes to the onset and progression of AD. It may suggest that the manipulation of LCN2 in the CNS would be a crucial target for regulation of the pathogenesis and risk of AD.
Alzheimer Disease ; Astrocytes ; Biological Processes ; Bone Marrow ; Brain ; Cell Movement ; Cell Survival ; Central Nervous System ; Diagnosis ; Epithelial Cells ; Glycoproteins ; In Vitro Techniques ; Inflammation ; Insulin Resistance ; Kidney ; Lipocalins ; Liver ; Microglia ; Neurons ; Prognosis ; Uterus

The hypothalamus is part of the diencephalon and has several nuclei, one of which is the arcuate nucleus. The arcuate nucleus of hypothalamus (ARH) consists of neuroendocrine neurons and centrally-projecting neurons. The ARH is the center where the homeostasis of nutrition/metabolism and reproduction are maintained. As such, dysfunction of the ARH can lead to disorders of nutrition/metabolism and reproduction. Here, we review various types of neurons in the ARH and several genetic disorders caused by mutations in the ARH.

Objective: Ischemic stroke and myocardial infarction are 2 of the leading causes of mortality. Both conditions are caused by arterial occlusion, resulting in ischemic necrosis of the cells in the cortex and heart. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs longer than 200 nucleotides without protein-coding potential. Thousands of lncRNAs have been identified but their involvement in ischemic stroke and myocardial infarction has not been studied extensively. Therefore, this study aimed to identify the role of lncRNAs, particularly those that are commonly altered in these two ischemic injuries. Methods: We combined diverse RNA sequencing data obtained from public databases and performed extensive bioinformatics analyses to determine reliable lncRNAs commonly identified from these datasets. Using sequence analysis, we also detected the lncRNAs that may act as microRNA (miRNA) regulators. Results: We found several altered lncRNAs that were common in ischemic stroke and myocardial infarction models. Some of these lncRNAs, including zinc finger NFX1-type containing 1 antisense RNA 1 and small nucleolar RNA host gene 1, were previously reported to be involved in the pathogenesis of each of these models. Interestingly, several lncRNAs had binding sites for miRNAs that were previously reported to be involved in the hypoxic response, suggesting the possible role of these lncRNAs as regulators in ischemic responses. Conclusion The lncRNAs identified in this study will be useful in determining the regulatory networks in ischemic stroke and myocardial infarction and in identifying potential specific markers for each of these ischemic diseases.

Vascular dementia (VaD) is the second most common type of dementia and is characterized by memory impairment, blood–brain barrier disruption, neuronal cell loss, glia activation, impaired synaptic plasticity, and cholinergic system abnormalities. To effectively prevent and treat VaD a good understanding of the mechanisms underlying its neuropathology is needed.Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor with multiple functions in the systemic circulation and the central nervous system and is known to regulate neuronal cell survival, synaptic formation, glia activation, and cognitive decline. Recent studies indicate that when compared with normal subjects, patients with VaD have low serum BDNF levels and that BDNF deficiency in the serum and cerebrospinal fluid is an important indicator of VaD. Here, we review current knowledge on the role of BDNF signaling in the pathology of VaD, such as cerebrovascular dysfunction, synaptic dysfunction, and cholinergic system impairment.

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol (25-200 µM) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis factor-α and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.
Apoptosis ; Brain-Derived Neurotrophic Factor ; Caspase 3 ; Cell Survival ; Cytokines ; Humans ; Inflammation ; Interleukin-10 ; Interleukin-4 ; Interleukins ; Macrophages* ; MAP Kinase Kinase Kinase 5 ; MicroRNAs ; Necrosis ; Oxidative Stress ; RNA, Messenger ; Sirtuin 1

Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation.
Autophagy* ; Central Nervous System Diseases ; Inflammation ; Microglia* ; MicroRNAs