Target For Schizophrenia Essay

Phosphodiesterase breaks phosphodiester bond and converts cAMP back to AMP, getting rid of second messenger

Cholinesterases are a group of enzymes present in mammals which breakdown certain neurotransmitters by hydrolyzing the ester bonds within a molecule (Rang & Dale, 2007). There are two major types of enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Though similar in structure, they differ in distribution, function and substrate specificity.

Second, in order to further confirm the information about characteristics and function of the targeting protein that we have

Figure 1.b shows the ‘Lock and Key’ model where two individual substrates meet the active site where

Inhibitors of phosphodiesterase type 4 (PDE4) act by increasing intracellular concentrations of cyclic adenosine monophosphate, which has a broad range of anti-inflammatory effects on various key effector cells involved in asthma and chronic obstructive pulmonary disease (COPD)

A study by Belujon and Anthony (2013) on the treatment of Parkinson’s disease (PD) and publications by Grilly (2002) suggests that patients with PD showed increased levels of dopamine secretion when given L-dopa, but consequentially started showing many symptoms of psychosis. The findings above indicate that increased levels of dopamine in the brain correlate to the varying symptoms of schizophrenia and psychosis (Belujon & Anthony, 2013; Grilly, 2002). However, studies by Bradford (2009) established that the use of antipsychotics, such as Phencyclidine (PCP) and Ketamine, produced decreased levels of glutamate in the brain’s cerebrospinal fluid, which have been shown to be involved in the development of schizophrenia. Furthermore, studies conducted on the human use of PCP and Ketamine have been found to cause positive symptoms of schizophrenia, psychosis and characteristics of cognitive defects (Howes & Kapur, 2009; Bradford,

A. SIGNIFICANCE. Our goal is to screen chemical libraries to identify compounds that modulate mitochondrial transport in hippocampal and cortical neurons. This study is significant in four ways: (1) There is an urgent need to develop CNS (Central Nervous System) active drugs. CNS disorders are not only staggeringly complex but are poorly treated diseases (Palmer and Stephenson, 2005). In the United States alone the annual cost for stroke, depression, Schizophrenia and Alzheimer’s disease are currently estimated to be over $250 billion annually (Pangalos et al., 2007). Despite the advances in translational medicine and pharmaceutical research little progress has been made in developing CNS therapeutics. Improving CNS drug discovery efforts is an urgent goal as an estimated 1.5 billion people suffer from CNS-related diseases worldwide. Unfortunately only a handful of new drugs have been brought to the market with very few in the pharmaceutical pipeline (Kissinger, 2011; Schoepp, 2011; Abbot, 2011). The majority of pharmaceutical companies have recently announced a shift from supporting internal drug discovery efforts in favor of academic and government partnerships (Schoepp, 2011). At Scripps Florida we have close interaction of state of the art high throughput small molecule screening and cutting-edge neuroscience research. Thus we are in a unique position to address the challenges in developing CNS therapeutics. (2) Mitochondrial dysfunction is part of the pathophysiology of

Pimavanserin (marketed as Nuplazid) is a drug developed and approved for the treatment of PDP by the FDA in April 2016. Its mechanism of action and therapeutic relevance is quite significant. As previously mentioned it is a non-dopaminergic second generation antipsychotic. It primarily exhibits selective inverse agonistic behaviours due to its high affinity on the 5-HT2A receptors (Ki 0.087nM) albeit low affinity on the 5-HT2C receptors (Ki 0.44nM) (Meltzer et al., 2012). Although it displays anti-hallucinogenic properties that assist in the overall alleviation of PDP, its mechanism of action is not completely understood to

Figure 1 Structure of G-protein-coupled receptor, showing alpha-helical proteins attached to the three subunits of the G-protein.

Approximately 22% of the American population suffers from some kind of mental disorder at any given time. (Passer and Smith, 2004) Schizophrenia is one of the most serious of these mental disorders, and there are many different kinds of treatment. While all mental disorders offer diagnosis and treatment challenges, few are more challenging than schizophrenia. It is both bizarre and puzzling, and has been described as “one of the most challenging disorders to treat effectively.” (Passer and Smith, 2004, 534)

Exploring Potential Parkinson’s Disease Therapies: The efficacy of Guanabenz and its derivatives as a therapy for attenuating ER stress-induced cell death in proteinopathies

Monoamine oxidases (MAOs) are FAD depending enzymes and exists in two forms, namely MAO-A and MAO-B. MAOs are responsible for the regulation and metabolism of major monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA). MAO-A preferentially oxidizes serotonin. Human MAO-A inhibitors are antidepressants and antianxiety agents [1].

Question 8: Antagonization of the ACh receptors needs to happen and the regeneration of cholinesterase to clear the ACh synapse.

For the second part of the experiment, one had to use the knowledge learn from viewing protein molecules in FirstGlance in Jmol to analyze the protein PDB ID: 4EEY. The analysis of this protein was done using the RSCB protein data bank (PDB) at (http://www.rcsb.org/pdb/home/home.do).2

Apremilast (CC-10004) is an oral phosphodiesterase 4 inhibitor. As the dominant phosphodiesterase expressed in immune cells, phosphodiesterase 4 degrades cyclic AMP into AMP. Phosphodiesterase 4 inhibition elevates intracellular cAMP, which can down-regulate the inflammatory responses via mechanisms including inhibiting inflammatory cytokine expression and increasing anti-inflammatory mediator expression.