From the tyrosine hydroxylase hypothesis of Parkinson's disease to modern strategies: a short historical overview.

A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical findings that orally given L-DOPA can alleviate or even prevent akinesia gave great hope for the treatment of PD. Attention focused on the role of tyrosine hydroxylase (TH) as the rate-limiting enzyme in the formation of catecholamines.

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer's Disease Hypothesis?

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer's disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism.

Neurotoxic effects of acrylamide on dopaminergic neurons in primary mesencephalic cell culture.

Introduction: Exposure to acrylamide is increasing worldwide as a result of its heavy use in industry and formation in carbohydrate-rich food cooked at high temperature. Despite its neurotoxicity, no studies have shown its toxic effects on dopaminergic neurons yet. Therefore, the current study was carried out to show whether acrylamide adversely affects primary cultured dopaminergic neurons.

Rotenone: from modelling to implication in Parkinson's disease.

Rotenone ([2R-(2α,6aα,12aα)]-1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-[1]benzopyran[3,4-b]furo [2,3-h][1]benzopyran-6(6aH)-one) is a naturally occurring compound derived from the roots and stems of Derris, Tephrosia, Lonchocarpus and Mundulea plant species. Since its discovery at the end of the 19th century, rotenone has been widely used as a pesticide for controlling insects, ticks and lice, and as a piscicide for management of nuisance fish in lakes and reservoirs. In 2000, Betarbet et al.

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease (AD), characterized by progressive cognitive impairment, memory loss, and thinking or speech problems. VaD is usually caused by cerebrovascular disease, during which, cerebrovascular endothelial cells (CECs) are vulnerable. CEC dysfunction occurs before the onset of VaD and can eventually lead to dysregulation of cerebral blood flow and blood-brain barrier damage, followed by the activation of glia and inflammatory environment in the brain.

The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson's disease.

Nuclear receptor-related factor 1 (Nurr1) has a crucial role in the development and maturation of mesencephalic dopamine (DA) neurons and also plays a protective role in maintenance of DA neurons by inhibiting the activation of microglia and astrocyte. Moreover, the mutations in Nurr1 gene are associated with familial Parkinson's disease (PD), suggested that Nurr1 modulation is a potential therapeutic target for PD. This study examines the therapeutic effects of transplantation of Nurr1 gene-modified bone marrow mesenchymal stem cells (MSCs) on 6-hydroxydopamine (6-OHDA)-induced PD rat models.

Long-term neurotoxic effects of domoic acid on primary dopaminergic neurons.

Domoic acid, an excitatory neurotoxin produced by certain algae, reaches the food chain through accumulation in some sea organisms. To investigate its long-term neurotoxicity on dopaminergic neurons, prepared primary mesencephalic cell cultures were exposed to different concentrations of domoic acid (0.1, 1, 10, 100 μM) on the 8th day in vitro (DIV) for 4 days.

Neurotoxic effects of domoic acid on dopaminergic neurons in primary mesencephalic cell culture.

Introduction: Domoic acid is a potent marine neurotoxin produced by certain species of the diatom genus Pseudonitzschia. To our knowledge, there are no studies that have investigated neurotoxic effects of domoic acid on dopaminergic neurons. Accordingly, the present study was carried out to investigate the potential neurotoxic effects of domoic acid on dopaminergic neurons in primary mesencephalic cell culture.

Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

Background: Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus.

Method: Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus.

Cytotoxic activities of flavonoids from a traditional Mongolian medicinal herb Clematis aethusifolia Turcz.

In the course of our search for antitumour constituents from the traditional Mongolian medicinal herb Clematis aethusifolia Turcz., 11 flavonoids were isolated for the first time from the dried aerial parts of the plant by flash C column chromatography, Sephadex LH-20 and reversed phase preparative HPLC. The planar structures of these flavonoids were established based on 1D and 2D NMR and high-resolution mass spectrometry.

Comparable Neuroprotective Effects of Pergolide and Pramipexole on Ferrous Sulfate-Induced Dopaminergic Cell Death in Cell Culture.

Background: Dopamine agonists are utilized clinically as an initial treatment in younger Parkinson's disease patients to delay the side effects associated with commencement of levodopa medication. These agonists also serveas adjunctive therapeutics with levodopa to lower the incidence of adverse motor symptoms in advanced stages of the disease.

Objectives: To compare the neuroprotective effects of the dopamine agonists pergolide and pramipexole on ferrous sulfate-induced neurotoxicity in dopaminergic neurons from primary mesencephalic cell culture.

Ganoderma Lucidum polysaccharides protect against MPP(+) and rotenone-induced apoptosis in primary dopaminergic cell cultures through inhibiting oxidative stress.

Oxidative stress plays a pivotal role in the progressive neurodegeneration in Parkinson's disease (PD) which is responsible for disabling motor abnormalities in more than 6.5 million people worldwide. Polysaccharides are the main active constituents from Ganoderma lucidum which is characterized with anti-oxidant, antitumor and immunostimulant properties.

Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson's disease.

Ginsenosides are the main active constituents of Panax ginseng. Ginsenoside Re is one of the major ginsenosides; whereas hydrolysis products such as Rd appear to have higher biological activity though are present in smaller amounts. Ginsenosides, from their early use in folk medicine to modern studies, appear to exert beneficial actions against aging and even neurodegenerative disorders.

Rapamycin protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture.

Introduction: Parkinson's disease is the most common movement disorder, characterized by a progressive and extensive loss of dopaminergic neurons in the substantia nigra pars compacta and their terminals in the striatum. So far, only symptomatic treatment is available, and no cure or disease-modifying drugs exist. The present study was designed to investigate the neuroprotective effect of rapamycin, an autophagy inducer, on dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture.

Neuroprotective role of thymoquinone against 1-methyl-4-phenylpyridinium-induced dopaminergic cell death in primary mesencephalic cell culture.

Objective: To investigate potential mechanisms mediating the neuroprotective effect of thymoquinone (TQ) on dopaminergic neurons.

Methods: This study was conducted in the Chemistry and Biochemistry Institute, University of Veterinary Medicine, Vienna, Austria between June and August 2013. Primary cultures were prepared from embryonic mouse mesencephala (OFI/SPF) at gestation day 14.

Recent advances in autophagy-based neuroprotection.

Macroautophagy is a highly regulated intracellular process that, under certain circumstances, delivers cytoplasmic components to the lysosomes for degradation. It consists of several sequential steps including initiation and nucleation, double membrane formation and elongation, formation and maturation of autophagosomes and finally autophagosomes/lysosomes fusion and degradation of intra-autophagosomal contents by lysosomal enzymes. After decades of considering autophagy as a cell death pathway, it has recently been shown to have a survival function through clearing of protein aggregates and damaged cytoplasmic organelles in response to a variety of stress conditions.

Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures.

Phytocannabinoids are potential candidates for neurodegenerative disease treatment. Nonetheless, the exact mode of action of major phytocannabinoids has to be elucidated, but both, receptor and non-receptor mediated effects are discussed. Focusing on the often presumed structure-affinity-relationship, Ki values of phytocannabinoids cannabidiol (CBD), cannabidivarin (CBDV), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), THC acid (THCA) and THC to human CB1 and CB2 receptors were detected by using competitive inhibition between radioligand [(3)H]CP-55,940 and the phytocannabinoids.

Neuroprotective effect of rotigotine against complex I inhibitors, MPP⁺ and rotenone, in primary mesencephalic cell culture.

Introduction: Dopamine agonists are suggested to be more efficacious in treating Parkinson's disease (PD) as they have neuroprotective properties in addition to their receptor-related actions.

Aim Of The Study: The present study was designed to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4-phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture relevant to PD.

Material And Methods: Primary mesencephalic cell cultures were prepared from embryonic mouse mesencephala at gestation day 14.

Nitric oxide production, systemic inflammation and lipid metabolism in periodontitis patients: possible gender aspect.

Aim: Nitric oxide (NO) plays a crucial role in vascular tone regulation and is involved in pathogenesis of periodontitis. In this cross-sectional study, we investigated the serum and saliva levels of NO metabolites in periodontal disease and their relationship with serum C-reactive protein (CRP) levels, lipids metabolism and periodontal disease severity.

Material And Methods: Serum and saliva were collected from non-smoking patients with generalized severe periodontitis (n = 89) and healthy controls (n = 56).

Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control.

Protective effects of resveratrol on glutamate-induced damages in murine brain cultures.

Resveratrol interacts with the complex III of the respiratory chain, is a radical scavenger and also suppressor of radical formation in the mitochondria. It reduces the intracellular calcium levels in pre- and postsynaptic neurons and also may inhibit the pro-apoptotic factors in glutamate overflow that occurs, e.g.

Recent advances in benefits and hazards of engineered nanoparticles.

Over recent decades, engineered nanoparticles are increasingly produced as the result of the rapid development in nanotechnology. They are currently used in a wide range of industrial and public sectors including healthcare, agriculture, transport, energy, materials, and information and communication technologies. As the result, an increasing concern has been raised over the potential impacts of engineered nanoparticles to human health.

Swainsonine as a lysosomal toxin affects dopaminergic neurons.

Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. When chronically ingested by livestock and wildlife, symptoms include severe neuronal disturbance. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal α-mannosidase (AMA) and accumulation of intracellular oligosaccharide.

Association between apolipoprotein E gene polymorphism and Alzheimer's disease in Uighur and Han populations.

Aim: Currently, there are almost 100 genes related to Alzheimer's disease (AD), and studies have indicated that apolipoprotein E (APO E) ε4 allele is a genetic risk factor of AD. However, there have been no reports of the distributions of APO E genotypes and allele frequencies in Uighur and Han AD patients.

Methods: We analyzed APO E gene polymorphism in 209 AD cases diagnosed based on National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association and 220 non-dementia controls.

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.