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Glial cells outnumber neurons in the brain and play important roles in the neuroinflammation that accompanies brain damage in neurodegenerative diseases. In Parkinson's disease (PD), dopaminergic neuronal loss is accompanied by inflammatory changes in microglia, astrocytes, innate immune cells, and infiltrating peripheral immune cells. Neuroinflammation is probably a fundamental immune response to protect neurons from harm and compensate for neuronal damage, but at the same time, its neurotoxic effects exacerbate neuron damage. Furthermore, neuroinflammatory response is regulated by immune cells, such as microglia, astrocytes, and peripheral immune cells, and by cytokines and chemokines. Accordingly, it is crucial that we understand how such immune cells in the brain regulate neuroinflammatory responses in PD pathology. This review describes the roles played by glia-mediated neuroinflammation in PD, both good and bad, and the therapeutic strategies used to treat PD. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an environmental toxin widely used in manufacturing industries. Studies conducted on the neurotoxicity of BPA demonstrated that at excessive, high concentrations (≥ 200 µM) adverse responses occurred which were not detectable using traditional toxicity tests at lower chemical quantities than 200 µM. Thus, a method capable of effectively detecting neurotoxicity at low concentrations (≤ 100 µM) was devised. Bisphenol A-mediated neurotoxicity was examined in primary cultured neurons using various methods, including Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity and reactive oxygen species assays. These methods confirmed BPA-induced toxicity at 200 μM, but no marked effect was observed at concentrations below 200 μM. However, when immunocytochemistry (ICC) was performed using a co-immunofluorescence assay of doublecortin (DCX) and microtubule-associated protein 2 (MAP2), BPA adversely affected neuronal maturation in neural progenitor cells at concentrations as low as 100 µM, at which the three traditional methods failed to detect any neurotoxic effect. Our DCX/MAP2 ICC findings indicate that low concentrations of BPA are toxic to developing neurons, and suggest that the devised double ICC technique might provide an effective means of assessing neurotoxic effects of environmental toxins at low concentrations. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease after Alzheimer's disease. PD exhibits clinical symptoms that include tremors, rigidity, and bradykinesia. Many drugs are available to treat PD, such as, l-dopa, COMT inhibitor, MAO-B inhibitor, and dopamine agonists, but these drugs simply compensate for dopamine loss in PD, and therefore, cannot completely suppress its symptoms or progression. Although the causes of PD are not clearly understood, common pathophysiological pathways, such as, oxidative stress, mitochondrial dysfunction, and neuroinflammation are considered to be etiological factors, and thus, many treatments and interventions have been developed to target these pathophysiological factors. This review describes the neuroprotective strategies devised based on current understanding of the pathophysiological mechanisms of PD. [ABSTRACT FROM AUTHOR]

Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a major risk factor underlying aging and the associated diseases of aging; of particular interest is insulin resistance during aging. Chronic inflammation impairs normal lipid accumulation, adipose tissue function, mitochondrial function, and causes endoplasmic reticulum (ER) stress, which lead to insulin resistance. However, some studies show that insulin resistance itself amplifies chronic inflammation. The activity of the insulin-dependent Akt signaling pathway is highlighted because of its decrease in insulin-sensitive organs, like liver and muscle, which may underlie insulin resistance and hyperinsulinemia, and its increased levels in non-metabolic organs, such as kidney and aorta. In that the prevalence of obesity has increased substantially for all age groups in recent years, our review summarizes the data showing the involvement of chronic inflammation in obesity-induced insulin resistance, which perpetuates reciprocal interactions between the chronic inflammatory process and increased adiposity, thereby accelerating the aging process. [ABSTRACT FROM AUTHOR]