Does Human Alpha-Synuclein Behave Like Prions?

Alpha-synuclein (α-synuclein) is a protein that is abundantly found in the brain and in a lesser amount in the heart and muscles. The exact role of α-synucleinis is not known, but it is considered to control the movement of synaptic vesicles. Its overexpression in the neurons leads to the formation of Lewy bodies that damage the dopaminergic neurons in the subtantianigra of the midbrain and leads to the progression of Parkinson's Disease (PD). There are evidences showing that aggregates of α-synuclein behave like prions. The present review is an attempt to put forth the nature of α-synuclein as prions.

Drosophila melanogaster a Versatile Model of Parkinson's Disease.

Parkinson's Disease (PD) is one of the most prevalent, recurrent and life-threatening neurodegenerative diseases. However, the precise mechanism underlying this disease is not yet clearly understood. For understanding the pathogenesis of PD, it is essential to identify the symptoms along with the novel biological markers and to develop strategies that could lead towards the development of effective therapy. PD is associated with Lewy bodies (LBs) formation and the loss of dopaminergic neurons in the substantia nigra pars compacta of mid brain region. For the improvement in treatment strategies, as well as understanding the pathophysiology of the PD in a number of animal models have been introduced that can recapitulate the pathophysiology, motor and nonmotor symptoms of PD. In contrast to mammalian models like rodents, mice and monkey, Drosophila is easy to handle as well as its maintenance cost is low. Due to the anatomical differences in the brain and other major organs of human and fly, the issues of standardizing the methods or experiments to analyze behavioral aspects (walking, writhing, eating and sleeping) are difficult in flies. The present review highlights the studies carried out for PD since 2000, using Drosophila melanogaster.

Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol.

Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, Multiple Sclerosis and Ischemic stroke have become a major health problem worldwide. Pre-clinical studies have demonstrated the beneficial effects of flavonoids on neurodegenerative diseases and suggest them to be used as therapeutic agents. Kaempferol is found in many plants such as tea, beans, broccoli, strawberries, and neuroprotective effects against the development of many neurodegenerative diseases such as Parkinson, Alzheimer's disease and Huntington's disease. The present study summarizes the neuroprotective effects of kaempferol in various models of neurodegenerative diseases. Kaempferol delays the initiation as well as the progression of neurodegenerative disorders by acting as a scavenger of free radicals and preserving the activity of various antioxidant enzymes. Kaempferol can cross the Blood-Brain Barrier (BBB), and therefore results in an enhanced protective effect. The multi-target property of kaempferol makes it a potential dietary supplement in preventing and treating neurodegenerative diseases.

Effect of capsaicin on the oxidative stress and dopamine content in the transgenic Drosophila model of Parkinson's disease.

In the present study the effect of capsaicin was studied on PD model flies expressing human alpha synuclein. First the potential of scavenging superoxide anion and free radicals by capsaicin at doses of 20, 40, 80 and 100 µM was estimated. The PD flies were allowed to feed separately on the diet containg 20, 40, 80 and 100 µM of capsaicin, respectively, for 24 days. After 24 days of exposure, fly head homogenate was prepared from each group and was used to estimate glutathione (GSH), protein carbonyl (PC), dopamine content, lipid peroxidation (LPO), glutathione-S-transferase (GST) and monoamine oxidase (MAO) activity. A dose dependent significant increase in the potential of scavenging superoxide anions and free radicals by capsaicin was observed for the doses of 20, 40, 80 and 100 µM. The exposure of capsaicin not only significantly increased the GSH (max. by 1.37-fold), and dopamine (max. by 1.56-fold) content but also reduced LPO (max. by 1.8-fold), GST (max. by 1.26-fold), MAO activities (max. by 1.60-fold) and PC content (max. by 1.95-fold), compared to unexposed PD flies (p < 0.05). The results suggest the protective role of capsaicin against the PD symptoms.

Antigenotoxic effect of the Plumbago zeylanica extract against the genotoxic damage induced by potassium canrenoate in cultured human peripheral blood lymphocytes.

In India, natural preparations derived from the plants are widely use for the treatments of various diseases. Hence, it becomes necessary to assess the modulating action of the plant extract when associated with other substances. Potassium canrenoate (PC) is a synthetic steroid and is used in the treatment of hypertension. It is not only a genotoxic agent, but also a tumor-initiating agent. In the present study, the effect of various doses (i.e., 5, 10, 20, and 30 µM) of PC were studied for their genotoxic effects in the presence of S9 mix in cultured human lymphocytes, using mitotic index, chromosomal aberrations, sister chromatid exchanges, and replication index as parameters. PC was found to be genotoxic at 20 and 30 µM. Treatment of 30 µM of PC was given along with different doses of Plumbago zeylanica extract (i.e., 107.5, 212.5, 315, and 417 µg/mL) of the culture medium. A dose-dependent decrease in the genotoxic effects of PC was observed. The result suggested that the plant extract per se does not have genotoxic potential, but can modulate the genotoxicity of PC in cultured human lymphocytes.