A review on neuropharmacological role of erucic acid: an omega-9 fatty acid from edible oils.

Neurodegenerative diseases (ND) are characterised by loss of neurons in the brain and spinal cord. For the normal functioning of the brain, divers group of fatty acids in the form of glycerophospholipids, glycerol ether lipids, cerebrosides, sulfatides, and gangliosides are essential. They are present abundantly in the nervous system and are actively involved in both the development and maintenance of the nervous system. A dietary deficiency of essential fatty acid during development results in hypomyelination state which affects various neuronal functions. Several studies suggested that age remains the primary risk factor for almost all neurodegenerative disorders. The potential contribution of these fatty acids in the progression of neurodegenerative disorders is indispensable. Erucic acid an omega 9 fatty acid, which is obtained from edible oils has proven to cause myocardial lipidosis, heart lesions and hepatic steatosis in animals therefore, its content in edible oils is restricted to certain levels by regulatory agencies. However, erucic acid in the form of a mixture with oleic acid is often used as a dietary treatment for the management of adrenoleukodystrophy without any cardiotoxicity. Our literature search revealed that, erucic acid reported to enhance cognitive function, interact with peroxisome proliferator activated receptors (PPARs), inhibit elastase and thrombin. In this review first we have attempted to describe the relationship between fatty acids and neurodegeneration followed by a description on the pharmacology of erucic acid. The overall purpose of this review is to analyse toxic and beneficial neuropharmacological effects of erucic acid.

Neuron-glia interactions: Molecular basis of alzheimer's disease and applications of neuroproteomics.

Neurodegenerative disorders present with progressive and irreversible degeneration of the neurons. Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting 50 million people worldwide (2017), expected to be doubled every 20 years. Primarily affected by age, AD is the cause for old-age dementia, progressive memory loss, dysfunctional thoughts, confusion, cognitive impairment and personality changes. Neuroglia formerly understood as "glue" of the brain neurons consists of macroglia (astrocytes and oligodendrocyte), microglia and progenitors NG2-glia, and constitute a large fraction of the mammalian brain. The primary functions of glial cells are to provide neurons with metabolic and structural support in the healthy brain; however, they attain a "reactive" state from the "resting" state upon challenged with a pathological insult such as a neurodegenerative cascade. Failure or defects in their homoeostatic functions (i.e. concentration of ions, neurotransmitters) ultimately jeopardize neurons with excitotoxicity and oxidative stress. Moreover, the most common clinical outcome of AD is the cognitive impairment and memory loss, which are attributed mainly by the accumulation of Aß. Failure of glial cells to remove the Aß toxic proteins accelerates the AD progression. The rapidly emerging proteomic techniques such as mass spectrometry (MS), cross-linking mass spectrometry, hydrogen deuterium trade mass spectrometry, protein foot printing and 2-DGE combined with LC-MS/MS present wide array of possibilities for the identification of differentially expressed proteins in AD.

Post-lesion administration of 7-NI attenuated motor and non-motor deficits in 6-OHDA induced bilaterally lesioned female rat model of Parkinson's disease.

The preoperative neuroprotective effect of the 7-nitroindazole (7-NI) in 6-hydroxydopamine (6-OHDA) induced unilateral male animal models of Parkinson's disease (PD) has been widely reported. However, the therapeutic approach to PD pathology would be closely associated with the post-lesion treatment by 7-NI in 6-OHDA-induced bilateral model. Also, there is a scarcity of data on neuroprotective effect of 7-NI in PD in females. We have studied the neuroprotective effects of 7-NI in 6-OHDA-induced bilaterally lesioned female rats after short-term post-lesion treatment. Sprague-Dawley female rats with bilateral intraventricular injection of either 6-OHDA (10.5µg) (n=8-11/group) or saline (sham; n=8/group) at substantia nigra (SN) were provided with 7-NI (30mg/kg/day) intraperitoneal, once a day during the 3 consecutive days of short term treatment. 6-OHDA lesioned animals developed the motor and non-motor deficits, which were evaluated by behavioral and neuro-biochemical tests from the substantia nigra. Post-lesion administration of 7-NI reduced the motor deficits induced by 6-OHDA in the behavioral tasks such as Rota rod, open field test and forced swim test. Simultaneously, the dopamine levels were restored by 7-NI in post lesion animals up to 76% in comparison to 6-OHDA lesioned animals (23%). Furthermore, antioxidant-like effect of 7-NI was observed in lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione tests. Conclusively, the present study showed that early postoperative administration of 7-NI attenuates the motor deficits induced by 6-OHDA in bilaterally lesioned female rat model of PD.

Plausible improvements for selective targeting of dopamine receptors in therapy of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative condition characterized by progressive and profound loss of dopaminergic neurons in the substantia nigra pars compacta leading to the formation of eosinophillic, intracytoplamic, proteinacious inclusions termed as lewy bodies. L-dopa remains as a gold standard for the treatment of PD, and is often combined with carbidopa to reduce the dose-limiting side effects. Long-term levodopa treatment is associated with the development of motor fluctuations and peak dose dyskinesias. Dopamine Replacement Therapy (DRT) with dopamine agonists (DAs) (ropinirole and pramipexole) is used to manage complications of L-dopa treatment, however, has been associated with numerous pharmacovigilence reports. The present review attempts to narrate the multiple receptor interaction of DAs followed by the assessment of their side effects during the treatment of PD and possible remedial strategy for selective targeting of dopamine receptors to overcome these affects in therapy of Parkinson's disease.

In silico study of naphtha [1, 2-d] thiazol-2-amine with adenosine A 2A receptor and its role in antagonism of haloperidol-induced motor impairments in mice.

Loss of dopaminergic nigrostriatal neurons in the substantia nigra leads to Parkinson's disease (PD). Adenosine A(2A) receptors (A(2A)Rs) have been anticipated as novel therapeutic target for PD. A(2A)Rs potentiate locomotor behavior and are predominantly expressed in striatum. Naphtha [1, 2-d] thiazol-2-amine (NATA), a tricyclic thiazole have been studied as new anti-Parkinsonian compound. AutoDock analysis and pharmacophore study of NATA with known A(2A)R antagonists explicit its efficacy as a possible adenosine receptor antagonist. In vivo pharmacology of NATA showed reduction of haloperidol (HAL)-induced motor impairments in Swiss albino male mice. Relatively elevated levels of dopamine in NATA pre-treated mice are suggestive of its possible role as neuromodulator in PD.